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SLPI (secretory leukocyte peptidase inhibitor)

Written2015-08Nella Ambrosi, Diego Guerrieri, Fiorella Caro, Micaela Barbieri Kennedy, Francisco Sánchez, Mercedes L. Sánchez, Eduardo Chuluyan
CEFYBO-CONICET, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina / echuluyan@fmed.uba.ar

Abstract Secretory Leukocyte Peptidase Inhibitor (SLPI) functionality in health and disease: Secretory Leukocyte Peptidase Inhibitor (SLPI) is a serine protease inhibitor of cathepsin G, trypsin and chymotrypsin, but primarily against neutrophil elastase. Its major function is to inhibit inflammation by blocking the proteolytic activity of these proteinases released by leukocytes and also through down-modulation of several cytokines. The anti-inflammatory activity is also mediated by inhibition of the activation of the transcription nuclear factor NF-kB. Some studies localized the molecule within the cytosol and in secondary granules of neutrophils. Because of this, it is believed that neutrophil-derived SLPI may regulate the protease/antiprotease balance at sites of tissue inflammation. In relation with the adaptive immune system, it was suggested that SLPI modulates the cellular and humoral immune response, by decreasing the T cell proliferation and reducing the class switching. Also, it is known that this polycationic non-glycosylated peptide, displays anti-microbial properties against bacteria, viruses (in particular HIV) and fungus. In summary, the SLPI is a pleitropic molecule, implicated in physiological and pathological events, such as wound healing, pregnancy, chronic obstructive pulmonary disease, cancer, ischemia reperfusion injury and stroke, among others. Their detection in serum and biological fluids may be useful as a biomarker to diagnosis and prognosis for certain diseases.

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Identity

Alias_namessecretory leukocyte protease inhibitor (antileukoproteinase)
Alias_symbol (synonym)HUSI-I
ALK1
ALP
BLPI
HUSI
WAP4
WFDC4
HGNC (Hugo) SLPI
LocusID (NCBI) 6590
Atlas_Id 46048
Location 20q13.12 chr20:43,881,055- 43,883,184 (reverse strand)  [Link to chromosome band 20q13]
Location_base_pair Starts at 43880880 and ends at 43883205 bp from pter ( according to hg19-Feb_2009)  [Mapping SLPI.png]
Fusion genes
(updated 2016)
C16orf74 (16q24.1) / SLPI (20q13.12)SEC14L2 (22q12.2) / SLPI (20q13.12)SLPI (20q13.12) / APPBP2 (17q23.2)
SLPI (20q13.12) / ARHGAP10 (4q31.23)SLPI (20q13.12) / LRP1 (12q13.3)SLPI (20q13.12) / SEC14L2 (22q12.2)

DNA/RNA

Description SLPI belongs to the whey acidic protein four-disulfide core family of proteins. The human SLPI gene is localized on chromosome 20q12-13.2 (Kikuchi et al. 1998). The SLPI gene consists of four exons and three introns, it spans approximately 2.6 kb (Kikuchi et al. 1998; Stetler et al. 1986). The SLPI gene is stable and seems to be nonpolymorphic (Abe et al. 1991). Though, it has the potential to be modulated at both the transcriptional and post-transcriptional levels (Abe et al. 1991). Up to date, it has not been detected a state of SLPI deficiency. However, patients with severe congenital neutropenia (a primary immunodeficiency syndrome characterized by mutations in at least 6 different genes) were found to have strongly reduced SLPI levels, being SLPI a key factor for the neutrophil differentiation in the bone marrow (Klimenkova et al. 2014).
Transcription The SLPI gene is actively transcribed in mucosal cells, being the half-life of the transcripts of approximately 12 h. Close to the exon 1, SLPI gene has four potential binding sites for transcription factor AP-1, three for AP-2 and one for C/EPB(Klimenkova et al. 2014). Also, Kikuchi et al., describes that SLPI has a promoter region which has a recognition sequence for two transcription factor, one of which is highly expressed in lung cell lines, and the other in nonlung cell lines (Kikuchi et al. 1997).

Protein

Description SLPI is an 11,7 kDa molecular weight non-glycosylated protein composed by 132 amino acids (Stolk et al. 1999). The amino acid sequence of SLPI generates a highly polycationic peptide with two highly homologous domains. These two domains (COOH and NH2 terminal domains) share around a 35% homology (Vogelmeier et al. 1996). Each domain contains eight cysteine residues that form four disulfide bonds, which helps to stabilize the structure of the molecule (Grutter et al. 1988). These cysteine rich domains are also called WAP domains (Whey Acid Protein). Domain 2 was initially described to bind and inhibit the serine proteases such as trypsin and elastase, while the domain 1 was probably not inhibitory (Eisenberg et al. 1990; Meckelein et al. 1990). It has been proposed that this last domain helps in the stabilization of the complexes "SLPI:elastase". Also, it is believed that the domain 1 mediates binding to heparin, and thus increases its antiprotease activity, probably as a result of a conformational change of the molecule. (Faller et al. 1992).
Expression SLPI was first isolated from bronchial secretions (Hochstrasser et al. 1972; Ohlsson et al. 1976). Then the SLPI was characterized by two groups of researchers, whom purified the molecule from the urine and (Seemuller et al. 1986) and the parotid gland secretions (Thompson et al. 1986). SLPI is located in both, the extracellular matrix and the intracellular compartments, suggesting that it could exert autocrine and paracrine effects (Taggart et al. 2005).
The expression of SLPI is constitutive as well as modulated by different factors. Constitutively SLPI can be found in serum and in extravascular mucosal fluids. Thus, it is found around of 40 (26.1-65.0) ng/ml in serum, 72 (0.4-250) ng/ml in bronchial lavage fluid (Hollander et al. 2007), in exhaled breath condensate (2.82 - 0.58 pg/ml)(Tateosian et al. 2012) and saliva (0.3-3.2 ug/ml) (Shugars et al. 2001). However, concentrations of the molecule vary depending on age and gender of the individual tested. In vivo, it is produced in the lung by tracheal serous glands and by clear bronchial cells. In male (Ohlsson et al. 1995) and female (Moriyama et al. 1999) genital tracts, SLPI is located in seminal plasma and cervical mucosa, respectively. Furthermore, it is produced by the parotid glands, intestinal epithelial cells (Si-Tahar et al. 2000), renal tubule cells (Ohlsson et al. 2001), keratinocytes (Wiedow et al. 1998), beta cells of the pancreas (Nystrom et al. 1999) and immune cells like neutrophils and alveolar macropaghes (Sallenave et al. 1997; Mihaila et al. 2001; Guerrieri et al. 2011).
The SLPI expression is modulated by different molecules. It has been shown that SLPI is up-regulated by LPS, IL-1beta, TNF-alpha, neutrophil elastasa, alpha-defensins, surfactant protein A, corticosteroid and progesterone (Sallenave et al. 1994; Reid et al. 1999; Maruyama et al. 1994; Abbinante-Nissen et al. 1995; King et al. 2003; Velarde et al. 2005; van Wetering et al. 2000; Ramadas et al. 2009). Finally, apoptotic cells can upregulate SLPI production by macrophages (Odaka et al. 2003). In contrast, few factors can downmodulate the expression of SLPI. Among them, the most significant are IFNgamma and TGF-beta (Jaumann et al. 2000; Jin et al. 1997).
Although, the structure of SLPI seems to be stable, it could be cleaved and inactive-ated by chymase(Belkowski et al. 2008), cathepsins B, L, S (Taggart et al. 2001), lipid peroxidation products (Tomova et al. 1994) and Host dust mite 1 allergen (Brown et al. 2003), among others(Weldon et al. 2009).
Function Antiprotease activity: The inhibition of protease activity was described for C-terminus domain against elastasa, cathepsin G, trypsin, chymotrypsin, tryptase and chymase (Williams et al. 2006). Thus, SLPI major function is inhibit inflammation by blocking the proteolytic activity of serine proteinases released by leukocytes and also through blocking the LPS effects, such as the upregulation of several cytokines like TNFalpha, MCP-1 and IL-6 (Yang et al. 2005; Jin et al. 1998; Taggart et al. 2005; Ashcroft et al. 2000). SLPI acts locally to maintain a protease/antiprotease balance thereby preventing protease mediated tissue destruction (Vogelmeier et al. 1990). In the lungs, the disturbance of this balance is responsible for various lung diseases, many of which are initiated and maintained by the recruitment and activation of neutrophils (Birrer et al. 1994; Suter 1989).
Anti-inflammatory activity:
SLPI has anti-inflammatory activities not necessarily related to its ability to inhibit extracellular proteases. The anti-inflammatory activity is also mediated by inhibition of proteolytic degradation of IkB, an inhibitor of the nuclear factor NF-kB (Ashcroft et al. 2000; Samsom et al. 2007). It has been shown that over-expression of SLPI inhibits NF-kB, which is a transcription factor of several pro-inflammatory mediators in pulmonary inflammation (Henriksen et al. 2004). Currently, there are some evidence that SLPI is rapidly taken up by cells and is localized in the nucleus and cytoplasm (Taggart et al. 2002). In the cytoplasm, SLPI prevents degradation of several key proteins in the regulated activation of NF-kB, as IkBalpha, IkBbeta and IRAK (IL-1-receptor-associated kinase) through the ubiquitin-proteasome mechanism (Greene et al. 2004; Taggart et al. 2002), that follows the activation of NF-kB by LPS or LTA (lipoteichoic acids). Also it has been proposed that SLPI acting in the nucleus can bind to NF-kB consensus region of target genes (Taggart et al. 2005). The entering into the nucleus occurs through a mechanism in which SLPI may traverse membranes, due to its cationic nature (favored by the high content of arginine and lysine) by interaction with the negatively charged membrane. Independently of the mode of action, in vivo experiments have demonstrated anti-inflammatory / pro-apoptotic activities in the lung, and in a variety of other organs.
Microbicidal activity:
Against Bacteria:
SLPI displays anti-microbial properties in vivo and in vitro (Sallenave 2002; Gomez et al. 2009). It has been recently reported that mouse and even human SLPI shows anti-bacterial activity against mycobacteria and it constitutes a pattern recognition receptor (PRR), that not only kills the microorganism, but also facilitates their phagocytosis by murine and human macrophages (Nishimura et al. 2008; Gomez et al. 2009). Either the antimicrobial activity or PRR ability depends on the COOH terminal domain where the inhibitory activity of serine proteases resides. The WAPs domains of the molecule are involved, and this is due to cationic residues that allow the disruption of the membranes of target organisms (Verma et al. 2007; Gomez et al. 2009; Nishimura et al. 2008). The antimicrobial activity of human SLPI has been described for various bacteria such as Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermis (Wiedow et al. 1998; Wingens et al. 1998), Mycobacterium tuberculosis (Gomez et al. 2009), and Escherichia coli (Williams et al. 2006). Therefore this activity is against Gram negative and Gram positive bacteria and is part of the defense system of the mucosa.
Against Viruses:
SLPI has been suggested as the main soluble factor responsible for the HIV inhibitory effect of saliva. It is well-established that human saliva inhibits HIV infectivity in vitro (McNeely et al. 1995; Nagashunmugam et al. 1997; Shugars et al. 2001; Malamud et al. 1992; Fultz 1986). The infection of adherent primary monocytes with HIV-1 was significantly suppressed in the presence of human saliva [76-80]. Four in vitro studies have demonstrated that SLPI has anti-HIV-1 activity in cells that included peripheral blood mononuclear cells, purified primary T cells, and SupT1 cells, a lymphocyte-derived tumor cell line (Fultz 1986; Hocini et al. 2000; Shugars et al. 1997; Skott et al. 2002). Evidence suggests that SLPI blocks HIV-1 internalization in a dose-dependent manner (McNeely et al. 1997). McNeely et al. found that SLPI inhibits a step of viral infection that occurs after virus binding but before reverse transcription. In a co-precipitation experiment, it was described a 55-kDa cell surface protein from monocytes by using anti-SLPI antibodies. For some authors, the interaction between HIV and CCR5 could be the main target of SLPI (Naif et al. 1998). Other authors showed that SLPI interferes with HIV fusion with the T-cell plasma membrane through binding to scramblase 1, a membrane protein that interacts with CD4 and controls the movement of the phospholipid bilayer of the plasma membrane (Shugars et al. 1999). It was also demonstrated that in myeloid cell, SLPI blocks viral entry/fusion as a result of binding to annexin II (Ohlsson et al. 2001; Ma et al. 2004; Drannik et al. 2011). This molecule is a macrophage receptor that binds to phosphatidylserine moiety that HIV carries on its outer layer on exiting from an infected cell (Ohlsson et al. 2001; Drannik et al. 2011; Ma et al. 2004). Furthermore, the elastase inhibiting activity of SLPI was not be essential for their anti-HIV-1 activity (McNeely et al. 1997).
Against Fungi:
C. albicans and Aspergillus fumigatus were sensitive to the antimicrobial activity of recombinant SLPI. This activity was localized to N-terminal domain of the molecule (Tomee et al. 1997).
Wound healing activity:
The role of SLPI in tissue repair was suggested by the observation that in human, epithelial expression of SLPI is increased in damaged skin (Wingens et al. 1998). Studies in SLPI deficient mice demonstrated that SLPI has an essential role in wound healing (Ashcroft et al. 2000). In the absence of SLPI, the animals presents a delay in cutaneous wound healing, which is attributed to an increased and prolonged inflammatory response during the repair process, and a delay in the accumulation of the matrix. The altered inflammatory profile involves enhanced activation of local TGF-beta (Ashcroft et al. 2000).
Immunomodulatory activity in adaptive immune response:
The effect of SLPI seems not to be limited to innate immune response but also to the cellular and humoral adaptive immune response. In fact, the high SLPI expression was found in dendritic cells of mucosal lymph node and it was suggested that these dendritic cells regulate cellular activation to microbial products and maintain the tolerance threshold (Samsom et al. 2007). Also, we have observed that SLPI decreases lymphocyte proliferation, a phenomenon which depends on the presence of monocytes (Guerrieri et al. 2011). However, it is not possible to rule out a direct effect of SLPI on lymphocytes since it is able to bind the receptors phospholipid scramblases 1 and 4 on CD4 T cells (Py et al. 2009). On tonsillar cells, SLPI inhibits B cells expressing activation-induced cytidine deaminase, an enzyme involved in class switching. Thus, the overall idea is that SLPI is a tolerigenic factor, that it is able to down modulate the innate and adaptive immune response. Moreover, recently it has been shown that the hyporesponsiveness of human buccal epithelium to microbial stimulation is a phenomenon that depends on SLPI expression. (Menckeberg et al. 2015).
Recently, it has been also described that SLPI, in conjunction of neutrophil DNA or cathepsin G and human neutrophil elastase, induced a marked production of type I interferon by plasmacytoid dendritic cells (Skrzeczynska-Moncznik et al. 2012; Skrzeczynska-Moncznik et al. 2013). On the other hand, it was found that SLPI inhibits the formation of neutrophil extracellular traps; structures that are involved in the elimination of microorganisms, and also in the presentation of autoantigens (Zabieglo et al. 2015). These findings suggest a role of SLPI in autoimmune diseases.

Implicated in

Note
Entity Cancer
Note The invasiveness of tumors occurs through infiltration of tumor cells into healthy tissue and by angiogenesis, which is modulated by proteases and antiproteases released from tumor cells that carry out tissue remodeling. Many studies have shown that SLPI expression is modulated in cancer. However, there has been reported an increased or decreased expression profile of the protein depending on the type of tumor. For example, SLPI expression is increased in pancreatic (Iacobuzio-Donahue et al. 2003), thyroid (Jarzab et al. 2005), cervix (Rein et al. 2004), endometrial (Zhang et al. 2002), ovarian (Israeli et al. 2005) and gastric cancer (Cheng et al. 2008). In contrast, it is weakly expressed in nasopharyngeal carcinoma (Sriuranpong et al. 2004; Huang et al. 2012), bladder tumors (Liang et al. 2002) and some breast carcinomas (Hu et al. 2004). As we mentioned above, in ovarian cancer, SLPI is over-expressed and is thought to have a carcinogenic function (Hough et al. 2001; Clauss et al. 2005; Devoogdt et al. 2009) independent of its antiprotease activity (Simpkins et al. 2008). However, in Lewis lung cancer cells, the pro-tumoral activity was shown to be dependent on its protease inhibitor activity (Devoogdt et al. 2003). Also, it was described that SLPI plasma levels were elevated in lung cancer patients (Zelvyte et al. 2004). More recently, low level of SLPI was detected in oral squamous cell carcinoma compared with normal oral epithelium (Wen et al. 2011). Moreover, an inverse correlation was also reported between SLPI and histological parameters associated with tumor progression (Wen et al. 2011). Interestingly, SLPI reduced the hepatic lung carcinoma metastasis (Wang et al. 2006). In breast tumors, the mRNA expression of SLPI either increases or decreases depending on the case (Kluger et al. 2004; Stoff-Khalili et al. 2005). Also in a breast tumor cell line, the SLPI overexpressing cells did not develop tumors in mice (Amiano et al. 2013). This effect was specific for this type of cell line, since colon tumor cells overexpressing SLPI, developed faster tumors than control cells. Moreover, the breast cancer cell line that overexpresses SLPI showed a decrease in E-cadherin expression, pro-apoptotic effects and cell cycle arrests. (Rosso et al. 2014). Interestingly, the administration of these SLPI transfected cells, which do not develop tumor in immunocompetent mice, inhibited the tumor growth and increased the survival of mice that were inoculated with mock transfected control cells. (Amiano et al. 2011).
In ovarian cancer SLPI inhibits cell growth through an apoptotic pathway (Nakamura et al. 2008), while, it has been also described that over-expression of SLPI is capable of producing a more aggressive ovarian cancer in vitro and in vivo models (Devoogdt et al. 2009). In fact, it was suggested that SLPI could be a useful diagnostic and prognostic tool in ovarian cancer (Carlson et al. 2013).
The SLPI gene and the protein expression are significantly lower in metastatic "head and neck squamous cell carcinoma" compared with non-metastatic ones. Also, an inverse significant correlation with HPV status was found for this kind of tumor (Hoffmann et al. 2013). Therefore, overall these data suggests us that it is not possible to generalize the findings related to SLPI expression and function in only a unique type of tumor, since its expression and modulation seems to be tumor specific.
  
Entity Pregnancy
Note SLPI among others antimicrobial peptides seems to play a role in pregnancy. SLPI is produced by amnion epithelium and deciduas (King et al. 2007). High levels of SLPI were found in the cervical mucus plug during human pregnancy. The SLPI mRNA expression was higher in the second and the third trimester when compared with the first one (Itaoka et al. 2015). Thus, in amniotic fluid, its concentration increases according to the period of pregnancy and the highest levels is reached on the onset of labor (Denison et al. 1999). As SLPI is a natural antimicrobial molecule, it may be involved in the prevention of uterine infection during pregnancy and labor, and be a modulator of inflammation in this stage.
  
Entity Autoimmunity
Note High levels of SLPI have been observed in several autoimmune diseases. For example, it was observed in: i) inflamed joint tissues in a rat model of arthritis (Song et al. 1999); ii) patients with primary Sjögren's syndrome (Maruyama et al. 1998); iii) immune cells infiltrating the corpus in autoimmune gastritis (Hritz et al. 2006); iv) macrophages, activated microglia, neuronal cells and astrocytes during experimental autoimmune encephalomyelitis (Mueller et al. 2008).
In contrast, the administration of systemic SLPI or microencapsulated SLPI has proven to reduce the injury found in tissues of different autoimmune models (Guazzone et al. 2011; Song et al. 1999). Overall, these results highlight the in vivo immunosuppressive effect of SLPI. However, it has been also implicated in the pathogenesis of other autoimmune diseases such as psoriasis. As we mentioned above, Nestle et al. have demonstrated that the IFNalpha, produced by plasmacytoid dendritic cells in response to DNA structures, containing the neutrophil serine protease cathepsin G (CatG) and SLPI was important in the development of psoriatic skin lesions (Skrzeczynska-Moncznik et al. 2013). In fact, the neutralization of SLPI reduces the severity of experimental autoimmune encephalitis (Muller et al. 2012).
  
Entity Tuberculosis
Note Exposure of murine peritoneal macrophages to Mycobacterium tuberculosis led to an increase in SLPI protein secretion (Ding et al. 2005) which seems to be a pattern recognition receptor for micobacterias and inhibits the growth of them(Nishimura et al. 2008; Gomez et al. 2009). In plasma of tuberculosis patients, the SLPI and IFN-gamma levels were significantly higher compared with the levels found in healthy subjects. Moreover, a direct association between SLPI levels and the severity of tuberculosis was detected. The main protective cytokine in tuberculosis, IFN-gamma, decreased the expression of SLPI in healthy subjects but not in tuberculosis patients, probably because of the low expression of IFN- gammaR detected in these patients (Tateosian et al. 2014).
  
Entity Chronic obstructive pulmonary disease (COPD)
Note Emphysema may be due to an imbalance in protease-antiprotease activity. Patients with COPD show high levels of SLPI compared with healthy subjects (Hollander et al. 2007). Conversely, SLPI levels are decreased during COPD exacerbations produced by bacterial infection or rhinovirus (Mallia et al. 2012).
  
Entity Ischemia reperfusion injury
Note It has been described a protective effect of SLPI in different ischemia/reperfusion injury models, such as heart and liver (Amberger et al. 2002; Lentsch et al. 1999). We have also observed a beneficial effect of SLPI in kidney ischemia reperfusion injury (unpublished result). Interestingly, in cardiac transplantation, null mice for SLPI had an impaired function after cold ischemia unlike the wild type (Schneeberger et al. 2008). Moreover, when SLPI was added to the preservation solution, myocardial contraction was restored to normal.
  
Entity Central Nervous System Ischemia
Note In two rat models, one of focal cerebral ischemia (Wang et al. 2003) and the other of spinal injury, it was observed high levels of SLPI. The same was seen in ischemic stroke in humans (Ilzecka et al. 2002). Interestingly, the administration of SLPI has been shown to be neuroprotective in both models of injury in rats (Wang et al. 2003; Hannila et al. 2013). Taking into account that the SLPI can promote axonal regeneration, plus the evidence of their neuroprotective effects, we could consider this molecule as potential therapeutic tool for different nervous system diseases (Hannila 2014).
  
Entity Biomarker
Note It has been found that the determination of serum SLPI levels could be useful as a marker of several diseases, such as disease activity in systemic sclerosis with interstitial lung disease (Aozasa et al. 2012). Also, it has been suggested that a form of cleaved SLPI can reflect the disease activity of patients with allergic rhinitis and asthma (Belkowski et al. 2009). It was also been proposed as a biomarker in ovarian and gastric cancer (Devoogdt et al. 2009; Cheng et al. 2008), or to identify subjects at risk of infections and malignant transformation due to HIV infection (Nittayananta et al. 2013). Recently, it was proposed as a biomarker for acute kidney injury after transplantation (Wilflingseder et al. 2014). However, until now none of these assays have been introduced in the clinical settings.
  

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Human papillomavirus infection in head and neck cancer: the role of the secretory leukocyte protease inhibitor
Hoffmann M, Quabius ES, Tribius S, Hebebrand L, Görögh T, Halec G, Kahn T, Hedderich J, Röcken C, Haag J, Waterboer T, Schmitt M, Giuliano AR, Kast WM
Oncol Rep 2013 May;29(5):1962-8
PMID 23467841
 
Plasma levels of alpha1-antichymotrypsin and secretory leukocyte proteinase inhibitor in healthy and chronic obstructive pulmonary disease (COPD) subjects with and without severe alpha1-antitrypsin deficiency
Hollander C, Westin U, Wallmark A, Piitulainen E, Sveger T, Janciauskiene SM
BMC Pulm Med 2007 Jan 29;7:1
PMID 17261175
 
Coordinately up-regulated genes in ovarian cancer
Hough CD, Cho KR, Zonderman AB, Schwartz DR, Morin PJ
Cancer Res 2001 May 15;61(10):3869-76
PMID 11358798
 
Secretory leukocyte protease inhibitor expression in various types of gastritis: a specific role of Helicobacter pylori infection
Hritz I, Kuester D, Vieth M, Herszenyi L, Stolte M, Roessner A, Tulassay Z, Wex T, Malfertheiner P
Eur J Gastroenterol Hepatol 2006 Mar;18(3):277-82
PMID 16462541
 
From mice to humans: identification of commonly deregulated genes in mammary cancer via comparative SAGE studies
Hu Y, Sun H, Drake J, Kittrell F, Abba MC, Deng L, Gaddis S, Sahin A, Baggerly K, Medina D, Aldaz CM
Cancer Res 2004 Nov 1;64(21):7748-55
PMID 15520179
 
Integrated analysis of multiple gene expression profiling datasets revealed novel gene signatures and molecular markers in nasopharyngeal carcinoma
Huang C, Tang H, Zhang W, She X, Liao Q, Li X, Wu M, Li G
Cancer Epidemiol Biomarkers Prev 2012 Jan;21(1):166-75
PMID 22068284
 
Increased serum levels of endogenous protectant secretory leukocyte protease inhibitor in acute ischemic stroke patients
Ińzecka J, Stelmasiak Z
Cerebrovasc Dis 2002;13(1):38-42
PMID 11810009
 
Highly expressed genes in pancreatic ductal adenocarcinomas: a comprehensive characterization and comparison of the transcription profiles obtained from three major technologies
Iacobuzio-Donahue CA, Ashfaq R, Maitra A, Adsay NV, Shen-Ong GL, Berg K, Hollingsworth MA, Cameron JL, Yeo CJ, Kern SE, Goggins M, Hruban RH
Cancer Res 2003 Dec 15;63(24):8614-22
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In silico chromosomal clustering of genes displaying altered expression patterns in ovarian cancer
Israeli O, Goldring-Aviram A, Rienstein S, Ben-Baruch G, Korach J, Goldman B, Friedman E
Cancer Genet Cytogenet 2005 Jul 1;160(1):35-42
PMID 15949568
 
Cervical Expression of Elafin and SLPI in Pregnancy and Their Association With Preterm Labor
Itaoka N, Nagamatsu T, Schust DJ, Ichikawa M, Sayama S, Iwasawa-Kawai Y, Kawana K, Yamashita T, Osuga Y, Fujii T
Am J Reprod Immunol 2015 Jun;73(6):536-44
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Gene expression profile of papillary thyroid cancer: sources of variability and diagnostic implications
Jarzab B, Wiench M, Fujarewicz K, Simek K, Jarzab M, Oczko-Wojciechowska M, Wloch J, Czarniecka A, Chmielik E, Lange D, Pawlaczek A, Szpak S, Gubala E, Swierniak A
Cancer Res 2005 Feb 15;65(4):1587-97
PMID 15735049
 
Transforming growth factor-beta1 is a potent inhibitor of secretory leukoprotease inhibitor expression in a bronchial epithelial cell line
Jaumann F, Elssner A, Mazur G, Dobmann S, Vogelmeier C
Munich Lung Transplant Group Eur Respir J
PMID 10885424
 
Lipopolysaccharide-related stimuli induce expression of the secretory leukocyte protease inhibitor, a macrophage-derived lipopolysaccharide inhibitor
Jin F, Nathan CF, Radzioch D, Ding A
Infect Immun 1998 Jun;66(6):2447-52
PMID 9596701
 
Secretory leukocyte protease inhibitor: a macrophage product induced by and antagonistic to bacterial lipopolysaccharide
Jin FY, Nathan C, Radzioch D, Ding A
Cell 1997 Feb 7;88(3):417-26
PMID 9039268
 
Structure of the murine secretory leukoprotease inhibitor (Slpi) gene and chromosomal localization of the human and murine SLPI genes
Kikuchi T, Abe T, Hoshi S, Matsubara N, Tominaga Y, Satoh K, Nukiwa T
Am J Respir Cell Mol Biol 1998 Dec;19(6):875-80
PMID 9843921
 
Innate immune defences in the human uterus during pregnancy
King AE, Kelly RW, Sallenave JM, Bocking AD, Challis JR
Placenta 2007 Nov-Dec;28(11-12):1099-106
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Differential regulation of secretory leukocyte protease inhibitor and elafin by progesterone
King AE, Morgan K, Sallenave JM, Kelly RW
Biochem Biophys Res Commun 2003 Oct 17;310(2):594-9
PMID 14521952
 
A lack of secretory leukocyte protease inhibitor (SLPI) causes defects in granulocytic differentiation
Klimenkova O, Ellerbeck W, Klimiankou M, Ünalan M, Kandabarau S, Gigina A, Hussein K, Zeidler C, Welte K, Skokowa J
Blood 2014 Feb 20;123(8):1239-49
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cDNA microarray analysis of invasive and tumorigenic phenotypes in a breast cancer model
Kluger HM, Kluger Y, Gilmore-Hebert M, DiVito K, Chang JT, Rodov S, Mironenko O, Kacinski BM, Perkins AS, Sapi E
Lab Invest 2004 Mar;84(3):320-31
PMID 14767486
 
Secretory leukocyte protease inhibitor in mice regulates local and remote organ inflammatory injury induced by hepatic ischemia/reperfusion
Lentsch AB, Yoshidome H, Warner RL, Ward PA, Edwards MJ
Gastroenterology 1999 Oct;117(4):953-61
PMID 10500079
 
Analysis of gene induction in human fibroblasts and bladder cancer cells exposed to the methylation inhibitor 5-aza-2'-deoxycytidine
Liang G, Gonzales FA, Jones PA, Orntoft TF, Thykjaer T
Cancer Res 2002 Feb 15;62(4):961-6
PMID 11861364
 
Inhibition of SLPI ameliorates disease activity in experimental autoimmune encephalomyelitis
Müller AM, Jun E, Conlon H, Sadiq SA
BMC Neurosci 2012 Mar 21;13:30
PMID 22436018
 
Secretory leukocyte protease inhibitor binds to annexin II, a cofactor for macrophage HIV-1 infection
Ma G, Greenwell-Wild T, Lei K, Jin W, Swisher J, Hardegen N, Wild CT, Wahl SM
J Exp Med 2004 Nov 15;200(10):1337-46
 
HIV in the oral cavity: virus, viral inhibitory activity, and antiviral antibodies: a review
Malamud D, Friedman HM
Crit Rev Oral Biol Med 1993;4(3-4):461-6
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Rhinovirus infection induces degradation of antimicrobial peptides and secondary bacterial infection in chronic obstructive pulmonary disease
Mallia P, Footitt J, Sotero R, Jepson A, Contoli M, Trujillo-Torralbo MB, Kebadze T, Aniscenko J, Oleszkiewicz G, Gray K, Message SD, Ito K, Barnes PJ, Adcock IM, Papi A, Stanciu LA, Elkin SL, Kon OM, Johnson M, Johnston SL
Am J Respir Crit Care Med 2012 Dec 1;186(11):1117-24
PMID 23024024
 
Increased serum concentrations of secretory leukoprotease inhibitor in patients with primary Sjögren's syndrome
Maruyama M, Sugiyama E, Hori T, Murayama R, Nakazaki S, Yamashita N, Kobayashi M
In Vivo 1998 Sep-Oct;12(5):535-8
PMID 9827363
 
Inhibition of human immunodeficiency virus type 1 infectivity by secretory leukocyte protease inhibitor occurs prior to viral reverse transcription
McNeely TB, Shugars DC, Rosendahl M, Tucker C, Eisenberg SP, Wahl SM
Blood 1997 Aug 1;90(3):1141-9
PMID 9242546
 
The location of inhibitory specificities in human mucus proteinase inhibitor (MPI): separate expression of the COOH-terminal domain yields an active inhibitor of three different proteinases
Meckelein B, Nikiforov T, Clemen A, Appelhans H
Protein Eng 1990 Jan;3(3):215-20
PMID 2158659
 
Human buccal epithelium acquires microbial hyporesponsiveness at birth, a role for secretory leukocyte protease inhibitor
Menckeberg CL, Hol J, Simons-Oosterhuis Y, Raatgeep HR, de Ruiter LF, Lindenbergh-Kortleve DJ, Korteland-van Male AM, El Aidy S, van Lierop PP, Kleerebezem M, Groeneweg M, Kraal G, Elink-Schuurman BE, de Jongste JC, Nieuwenhuis EE, Samsom JN
Gut 2015 Jun;64(6):884-93
PMID 25056659
 
Human alveolar macrophages express elafin and secretory leukocyte protease inhibitor
Mihaila A, Tremblay GM
Z Naturforsch C 2001 Mar-Apr;56(3-4):291-7
PMID 11371023
 
Secretory leukocyte protease inhibitor (SLPI) concentrations in cervical mucus of women with normal menstrual cycle
Moriyama A, Shimoya K, Ogata I, Kimura T, Nakamura T, Wada H, Ohashi K, Azuma C, Saji F, Murata Y
Mol Hum Reprod 1999 Jul;5(7):656-61
PMID 10381821
 
Novel role for SLPI in MOG-induced EAE revealed by spinal cord expression analysis
Mueller AM, Pedré X, Stempfl T, Kleiter I, Couillard-Despres S, Aigner L, Giegerich G, Steinbrecher A
J Neuroinflammation 2008 May 26;5:20
PMID 18501024
 
Human submandibular saliva inhibits human immunodeficiency virus type 1 infection by displacing envelope glycoprotein gp120 from the virus
Nagashunmugam T, Malamud D, Davis C, Abrams WR, Friedman HM
J Infect Dis 1998 Dec;178(6):1635-41
PMID 9815215
 
CCR5 expression correlates with susceptibility of maturing monocytes to human immunodeficiency virus type 1 infection
Naif HM, Li S, Alali M, Sloane A, Wu L, Kelly M, Lynch G, Lloyd A, Cunningham AL
J Virol 1998 Jan;72(1):830-6
PMID 9420295
 
Secretory leukoprotease inhibitor inhibits cell growth through apoptotic pathway on ovarian cancer
Nakamura K, Takamoto N, Hongo A, Kodama J, Abrzua F, Nasu Y, Kumon H, Hiramatsu Y
Oncol Rep 2008 May;19(5):1085-91
PMID 18425362
 
Potent antimycobacterial activity of mouse secretory leukocyte protease inhibitor
Nishimura J, Saiga H, Sato S, Okuyama M, Kayama H, Kuwata H, Matsumoto S, Nishida T, Sawa Y, Akira S, Yoshikai Y, Yamamoto M, Takeda K
J Immunol 2008 Mar 15;180(6):4032-9
PMID 18322212
 
Expression of oral secretory leukocyte protease inhibitor in HIV-infected subjects with long-term use of antiretroviral therapy
Nittayananta W, Kemapunmanus M, Yangngam S, Talungchit S, Sriplung H
J Oral Pathol Med 2013 Mar;42(3):208-15
PMID 23126266
 
Production of secretory leucocyte protease inhibitor (SLPI) in human pancreatic beta-cells
Nyström M, Bergenfeldt M, Ljungcrantz I, Lindeheim A, Ohlsson K
Mediators Inflamm 1999;8(3):147-51
PMID 10704052
 
Murine macrophages produce secretory leukocyte protease inhibitor during clearance of apoptotic cells: implications for resolution of the inflammatory response
Odaka C, Mizuochi T, Yang J, Ding A
J Immunol 2003 Aug 1;171(3):1507-14
PMID 12874244
 
Secretory leucocyte protease inhibitor in the male genital tract: PSA-induced proteolytic processing in human semen and tissue localization
Ohlsson K, Bjartell A, Lilja H
J Androl 1995 Jan-Feb;16(1):64-74
PMID 7539415
 
Inhibition of elastase from granulocytes by the low molecular weight bronchial protease inhibitor
Ohlsson K, Tegner H
Scand J Clin Lab Invest 1976 Sep;36(5):437-45
PMID 185683
 
Novel distribution of the secretory leucocyte proteinase inhibitor in kidney
Ohlsson S, Ljungkrantz I, Ohlsson K, Segelmark M, Wieslander J
Mediators Inflamm 2001 Dec;10(6):347-50
PMID 11817677
 
The phospholipid scramblases 1 and 4 are cellular receptors for the secretory leukocyte protease inhibitor and interact with CD4 at the plasma membrane
Py B, Basmaciogullari S, Bouchet J, Zarka M, Moura IC, Benhamou M, Monteiro RC, Hocini H, Madrid R, Benichou S
PLoS One 2009;4(3):e5006
PMID 19333378
 
Surfactant protein A enhances production of secretory leukoprotease inhibitor and protects it from cleavage by matrix metalloproteinases
Ramadas RA, Wu L, LeVine AM
J Immunol 2009 Feb 1;182(3):1560-7
PMID 19155504
 
Human neutrophil elastase regulates the expression and secretion of elafin (elastase-specific inhibitor) in type II alveolar epithelial cells
Reid PT, Marsden ME, Cunningham GA, Haslett C, Sallenave JM
FEBS Lett 1999 Aug 20;457(1):33-7
PMID 10486558
 
Evaluation of tissue-specific promoters in carcinomas of the cervix uteri
Rein DT, Breidenbach M, Nettelbeck DM, Kawakami Y, Siegal GP, Huh WK, Wang M, Hemminki A, Bauerschmitz GJ, Yamamoto M, Adachi Y, Takayama K, Dall P, Curiel DT
J Gene Med 2004 Nov;6(11):1281-9
PMID 15368588
 
Secretory Leukocyte Protease Inhibitor (SLPI) expression downregulates E-cadherin, induces -catenin re-localisation and triggers apoptosis-related events in breast cancer cells
Rosso M, Lapyckyj L, Amiano N, Besso MJ, Sánchez M, Chuluyan E, Vazquez-Levin MH
Biol Cell 2014 Sep;106(9):308-22
PMID 25039920
 
Antimicrobial activity of antiproteinases
Sallenave JM
Biochem Soc Trans 2002 Apr;30(2):111-5
PMID 12023836
 
Secretory leukoprotease inhibitor in mucosal lymph node dendritic cells regulates the threshold for mucosal tolerance
Samsom JN, van der Marel AP, van Berkel LA, van Helvoort JM, Simons-Oosterhuis Y, Jansen W, Greuter M, Nelissen RL, Meeuwisse CM, Nieuwenhuis EE, Mebius RE, Kraal G
J Immunol 2007 Nov 15;179(10):6588-95
PMID 17982048
 
The effect of secretory leukocyte protease inhibitor (SLPI) on ischemia/reperfusion injury in cardiac transplantation
Schneeberger S, Hautz T, Wahl SM, Brandacher G, Sucher R, Steinmassl O, Steinmassl P, Wright CD, Obrist P, Werner ER, Mark W, Troppmair J, Margreiter R, Amberger A
Am J Transplant 2008 Apr;8(4):773-82
PMID 18294346
 
The acid-stable proteinase inhibitor of human mucous secretions (HUSI-I, antileukoprotease)
Seemüller U, Arnhold M, Fritz H, Wiedenmann K, Machleidt W, Heinzel R, Appelhans H, Gassen HG, Lottspeich F
Complete amino acid sequence as revealed by protein and cDNA sequencing and structural homology to whey proteins and Red Sea turtle proteinase inhibitor FEBS Lett
PMID 3485543
 
Salivary concentration of secretory leukocyte protease inhibitor, an antimicrobial protein, is decreased with advanced age
Shugars DC, Watkins CA, Cowen HJ
Gerontology 2001 Sep-Oct;47(5):246-53
PMID 11490143
 
Constitutive and regulated secretion of secretory leukocyte proteinase inhibitor by human intestinal epithelial cells
Si-Tahar M, Merlin D, Sitaraman S, Madara JL
Gastroenterology 2000 Jun;118(6):1061-71
PMID 10833481
 
The alarm anti-protease, secretory leukocyte protease inhibitor, is a proliferation and survival factor for ovarian cancer cells
Simpkins FA, Devoogdt NM, Rasool N, Tchabo NE, Alejandro EU, Kamrava MM, Kohn EC
Carcinogenesis 2008 Mar;29(3):466-72
PMID 17916899
 
Inhibitory function of secretory leukocyte proteinase inhibitor (SLPI) in human saliva is HIV-1 specific and varies with virus tropism
Skott P, Lucht E, Ehnlund M, Björling E
Oral Dis 2002 May;8(3):160-7
PMID 12108760
 
DNA structures decorated with cathepsin G/secretory leukocyte proteinase inhibitor stimulate IFNI production by plasmacytoid dendritic cells
Skrzeczynska-Moncznik J, Wlodarczyk A, Banas M, Kwitniewski M, Zabieglo K, Kapinska-Mrowiecka M, Dubin A, Cichy J
Am J Clin Exp Immunol 2013 Jun 15;2(2):186-94
PMID 23885335
 
Secretory leukocyte protease inhibitor suppresses the inflammation and joint damage of bacterial cell wall-induced arthritis
Song Xy, Zeng L, Jin W, Thompson J, Mizel DE, Lei K, Billinghurst RC, Poole AR, Wahl SM
J Exp Med 1999 Aug 16;190(4):535-42
PMID 10449524
 
Global gene expression profile of nasopharyngeal carcinoma by laser capture microdissection and complementary DNA microarrays
Sriuranpong V, Mutirangura A, Gillespie JW, Patel V, Amornphimoltham P, Molinolo AA, Kerekhanjanarong V, Supanakorn S, Supiyaphun P, Rangdaeng S, Voravud N, Gutkind JS
Clin Cancer Res 2004 Aug 1;10(15):4944-58
PMID 15297395
 
Isolation and sequence of a human gene encoding a potent inhibitor of leukocyte proteases
Stetler G, Brewer MT, Thompson RC
Nucleic Acids Res 1986 Oct 24;14(20):7883-96
PMID 3640338
 
Preclinical evaluation of transcriptional targeting strategies for carcinoma of the breast in a tissue slice model system
Stoff-Khalili MA, Stoff A, Rivera AA, Banerjee NS, Everts M, Young S, Siegal GP, Richter DF, Wang M, Dall P, Mathis JM, Zhu ZB, Curiel DT
Breast Cancer Res 2005;7(6):R1141-52
PMID 16457694
 
The imbalance between granulocyte neutral proteases and antiproteases in bronchial secretions from patients with cystic fibrosis
Suter S
Antibiot Chemother (1971) 1989;42:158-68
PMID 2688542
 
Secretory leucoprotease inhibitor binds to NF-kappaB binding sites in monocytes and inhibits p65 binding
Taggart CC, Cryan SA, Weldon S, Gibbons A, Greene CM, Kelly E, Low TB, O'neill SJ, McElvaney NG
J Exp Med 2005 Dec 19;202(12):1659-68
PMID 16352738
 
The impact of IFN- receptor on SLPI expression in active tuberculosis: association with disease severity
Tateosian NL, Pasquinelli V, Hernández Del Pino RE, Ambrosi N, Guerrieri D, Pedraza-Sánchez S, Santucci N, D'Attilio L, Pellegrini J, Araujo-Solis MA, Musella RM, Palmero DJ, Hernandez-Pando R, Garcia VE, Chuluyan HE
Am J Pathol 2014 May;184(5):1268-73
PMID 24606882
 
Isolation, properties, and complete amino acid sequence of human secretory leukocyte protease inhibitor, a potent inhibitor of leukocyte elastase
Thompson RC, Ohlsson K
Proc Natl Acad Sci U S A 1986 Sep;83(18):6692-6
PMID 3462719
 
Antileukoprotease: an endogenous protein in the innate mucosal defense against fungi
Tomee JF, Hiemstra PS, Heinzel-Wieland R, Kauffman HF
J Infect Dis 1997 Sep;176(3):740-7
PMID 9291323
 
Selective oxidation of methionyl residues in the human recombinant secretory leukocyte proteinase inhibitor
Tomova S, Cutruzzolà F, Barra D, Amiconi G, Ascenzi P, Djinović Carugo K, Menegatti E, Sarti P, Schnebli HP, Bolognesi M
Effect on the inhibitor binding properties J Mol Recognit
PMID 7986566
 
The secretory leukocyte protease inhibitor gene is a target of epidermal growth factor receptor action in endometrial epithelial cells
Velarde MC, Parisek SI, Eason RR, Simmen FA, Simmen RC
J Endocrinol 2005 Jan;184(1):141-51
PMID 15642791
 
Defensins: antimicrobial peptides for therapeutic development
Verma C, Seebah S, Low SM, Zhou L, Liu SP, Li J, Beuerman RW
Biotechnol J 2007 Nov;2(11):1353-9
PMID 17886240
 
Use of secretory leukoprotease inhibitor to augment lung antineutrophil elastase activity
Vogelmeier C, Gillissen A, Buhl R
Chest 1996 Dec;110(6 Suppl):261S-266S
PMID 8989162
 
The secretory leukocyte protease inhibitor is a type 1 insulin-like growth factor receptor-regulated protein that protects against liver metastasis by attenuating the host proinflammatory response
Wang N, Thuraisingam T, Fallavollita L, Ding A, Radzioch D, Brodt P
Cancer Res 2006 Mar 15;66(6):3062-70
PMID 16540655
 
Up-regulation of secretory leukocyte protease inhibitor (SLPI) in the brain after ischemic stroke: adenoviral expression of SLPI protects brain from ischemic injury
Wang X, Li X, Xu L, Zhan Y, Yaish-Ohad S, Erhardt JA, Barone FC, Feuerstein GZ
Mol Pharmacol 2003 Oct;64(4):833-40
PMID 14500739
 
Decreased levels of secretory leucoprotease inhibitor in the Pseudomonas-infected cystic fibrosis lung are due to neutrophil elastase degradation
Weldon S, McNally P, McElvaney NG, Elborn JS, McAuley DF, Wartelle J, Belaaouaj A, Levine RL, Taggart CC
J Immunol 2009 Dec 15;183(12):8148-56
PMID 20007580
 
Secretory leukocyte protease inhibitor (SLPI) expression and tumor invasion in oral squamous cell carcinoma
Wen J, Nikitakis NG, Chaisuparat R, Greenwell-Wild T, Gliozzi M, Jin W, Adli A, Moutsopoulos N, Wu T, Warburton G, Wahl SM
Am J Pathol 2011 Jun;178(6):2866-78
PMID 21641406
 
Antileukoprotease in human skin: an antibiotic peptide constitutively produced by keratinocytes
Wiedow O, Harder J, Bartels J, Streit V, Christophers E
Biochem Biophys Res Commun 1998 Jul 30;248(3):904-9
PMID 9704025
 
Molecular pathogenesis of post-transplant acute kidney injury: assessment of whole-genome mRNA and miRNA profiles
Wilflingseder J, Sunzenauer J, Toronyi E, Heinzel A, Kainz A, Mayer B, Perco P, Telkes G, Langer RM, Oberbauer R
PLoS One 2014 Aug 5;9(8):e104164
PMID 25093671
 
SLPI and elafin: one glove, many fingers
Williams SE, Brown TI, Roghanian A, Sallenave JM
Clin Sci (Lond) 2006 Jan;110(1):21-35
PMID 16336202
 
Induction of SLPI (ALP/HUSI-I) in epidermal keratinocytes
Wingens M, van Bergen BH, Hiemstra PS, Meis JF, van Vlijmen-Willems IM, Zeeuwen PL, Mulder J, Kramps HA, van Ruissen F, Schalkwijk J
J Invest Dermatol 1998 Dec;111(6):996-1002
PMID 9856807
 
Suppression of macrophage responses to bacterial lipopolysaccharide (LPS) by secretory leukocyte protease inhibitor (SLPI) is independent of its anti-protease function
Yang J, Zhu J, Sun D, Ding A
Biochim Biophys Acta 2005 Sep 30;1745(3):310-7
PMID 16112212
 
The inhibitory effect of secretory leukocyte protease inhibitor (SLPI) on formation of neutrophil extracellular traps
Zabieglo K, Majewski P, Majchrzak-Gorecka M, Wlodarczyk A, Grygier B, Zegar A, Kapinska-Mrowiecka M, Naskalska A, Pyrc K, Dubin A, Wahl SM, Cichy J
J Leukoc Biol 2015 Jul;98(1):99-106
PMID 25917460
 
Increased plasma levels of serine proteinase inhibitors in lung cancer patients
Zelvyte I, Wallmark A, Piitulainen E, Westin U, Janciauskiene S
Anticancer Res 2004 Jan-Feb;24(1):241-7
PMID 15015603
 
Secretory leukocyte protease inhibitor mediates proliferation of human endometrial epithelial cells by positive and negative regulation of growth-associated genes
Zhang D, Simmen RC, Michel FJ, Zhao G, Vale-Cruz D, Simmen FA
J Biol Chem 2002 Aug 16;277(33):29999-30009
PMID 12023969
 
Regulation of SLPI and elafin release from bronchial epithelial cells by neutrophil defensins
van Wetering S, van der Linden AC, van Sterkenburg MA, de Boer WI, Kuijpers AL, Schalkwijk J, Hiemstra PS
Am J Physiol Lung Cell Mol Physiol 2000 Jan;278(1):L51-8
PMID 10645890
 

Citation

This paper should be referenced as such :
Ambrosi N, Guerrieri D, Caro F, Barbieri Kennedy M, Sánchez F, Sánchez ML, Chuluyan E
SLPI (secretory leukocyte peptidase inhibitor);
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Genes/SLPIID46048ch20q13.html


External links

Nomenclature
HGNC (Hugo)SLPI   11092
Cards
AtlasSLPIID46048ch20q13.txt
Entrez_Gene (NCBI)SLPI  6590  secretory leukocyte peptidase inhibitor
AliasesALK1; ALP; BLPI; HUSI; 
HUSI-I; MPI; WAP4; WFDC4
GeneCards (Weizmann)SLPI
Ensembl hg19 (Hinxton)ENSG00000124107 [Gene_View]  chr20:43880880-43883205 [Contig_View]  SLPI [Vega]
Ensembl hg38 (Hinxton)ENSG00000124107 [Gene_View]  chr20:43880880-43883205 [Contig_View]  SLPI [Vega]
ICGC DataPortalENSG00000124107
TCGA cBioPortalSLPI
AceView (NCBI)SLPI
Genatlas (Paris)SLPI
WikiGenes6590
SOURCE (Princeton)SLPI
Genetics Home Reference (NIH)SLPI
Genomic and cartography
GoldenPath hg19 (UCSC)SLPI  -     chr20:43880880-43883205 -  20q13.12   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)SLPI  -     20q13.12   [Description]    (hg38-Dec_2013)
EnsemblSLPI - 20q13.12 [CytoView hg19]  SLPI - 20q13.12 [CytoView hg38]
Mapping of homologs : NCBISLPI [Mapview hg19]  SLPI [Mapview hg38]
OMIM107285   
Gene and transcription
Genbank (Entrez)AF114471 AK312192 AX772818 BC020708 DQ891365
RefSeq transcript (Entrez)NM_003064
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)SLPI
Cluster EST : UnigeneHs.517070 [ NCBI ]
CGAP (NCI)Hs.517070
Alternative Splicing GalleryENSG00000124107
Gene ExpressionSLPI [ NCBI-GEO ]   SLPI [ EBI - ARRAY_EXPRESS ]   SLPI [ SEEK ]   SLPI [ MEM ]
Gene Expression Viewer (FireBrowse)SLPI [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)6590
GTEX Portal (Tissue expression)SLPI
Protein : pattern, domain, 3D structure
UniProt/SwissProtP03973   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP03973  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP03973
Splice isoforms : SwissVarP03973
PhosPhoSitePlusP03973
Domaine pattern : Prosite (Expaxy)WAP (PS51390)   
Domains : Interpro (EBI)ALP    WAP_dom   
Domain families : Pfam (Sanger)WAP (PF00095)   
Domain families : Pfam (NCBI)pfam00095   
Domain families : Smart (EMBL)WAP (SM00217)  
Conserved Domain (NCBI)SLPI
DMDM Disease mutations6590
Blocks (Seattle)SLPI
PDB (SRS)2Z7F    4DOQ   
PDB (PDBSum)2Z7F    4DOQ   
PDB (IMB)2Z7F    4DOQ   
PDB (RSDB)2Z7F    4DOQ   
Structural Biology KnowledgeBase2Z7F    4DOQ   
SCOP (Structural Classification of Proteins)2Z7F    4DOQ   
CATH (Classification of proteins structures)2Z7F    4DOQ   
SuperfamilyP03973
Human Protein AtlasENSG00000124107
Peptide AtlasP03973
HPRD00121
IPIIPI00008580   
Protein Interaction databases
DIP (DOE-UCLA)P03973
IntAct (EBI)P03973
FunCoupENSG00000124107
BioGRIDSLPI
STRING (EMBL)SLPI
ZODIACSLPI
Ontologies - Pathways
QuickGOP03973
Ontology : AmiGOendopeptidase inhibitor activity  serine-type endopeptidase inhibitor activity  protein binding  extracellular space  immune response  negative regulation of endopeptidase activity  antibacterial humoral response  antibacterial humoral response  enzyme binding  extracellular matrix  negative regulation of protein binding  response to lipopolysaccharide  negative regulation of viral genome replication  innate immune response  extracellular exosome  
Ontology : EGO-EBIendopeptidase inhibitor activity  serine-type endopeptidase inhibitor activity  protein binding  extracellular space  immune response  negative regulation of endopeptidase activity  antibacterial humoral response  antibacterial humoral response  enzyme binding  extracellular matrix  negative regulation of protein binding  response to lipopolysaccharide  negative regulation of viral genome replication  innate immune response  extracellular exosome  
Pathways : BIOCARTAProepithelin Conversion to Epithelin and Wound Repair Control [Genes]   
REACTOMEP03973 [protein]
REACTOME PathwaysR-HSA-6798695 [pathway]
NDEx NetworkSLPI
Atlas of Cancer Signalling NetworkSLPI
Wikipedia pathwaysSLPI
Orthology - Evolution
OrthoDB6590
GeneTree (enSembl)ENSG00000124107
Phylogenetic Trees/Animal Genes : TreeFamSLPI
HOVERGENP03973
HOGENOMP03973
Homologs : HomoloGeneSLPI
Homology/Alignments : Family Browser (UCSC)SLPI
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerSLPI [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)SLPI
dbVarSLPI
ClinVarSLPI
1000_GenomesSLPI 
Exome Variant ServerSLPI
ExAC (Exome Aggregation Consortium)SLPI (select the gene name)
Genetic variants : HAPMAP6590
Genomic Variants (DGV)SLPI [DGVbeta]
DECIPHER (Syndromes)20:43880880-43883205  ENSG00000124107
CONAN: Copy Number AnalysisSLPI 
Mutations
ICGC Data PortalSLPI 
TCGA Data PortalSLPI 
Broad Tumor PortalSLPI
OASIS PortalSLPI [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICSLPI  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDSLPI
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch SLPI
DgiDB (Drug Gene Interaction Database)SLPI
DoCM (Curated mutations)SLPI (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)SLPI (select a term)
intoGenSLPI
NCG5 (London)SLPI
Cancer3DSLPI(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM107285   
Orphanet
MedgenSLPI
Genetic Testing Registry SLPI
NextProtP03973 [Medical]
TSGene6590
GENETestsSLPI
Huge Navigator SLPI [HugePedia]
snp3D : Map Gene to Disease6590
BioCentury BCIQSLPI
ClinGenSLPI
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD6590
Chemical/Pharm GKB GenePA35944
Clinical trialSLPI
Miscellaneous
canSAR (ICR)SLPI (select the gene name)
Probes
Litterature
PubMed119 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineSLPI
EVEXSLPI
GoPubMedSLPI
iHOPSLPI
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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