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IL1B (interleukin 1, beta)

Identity

Other namesCatabolin
IL-1
IL-1B
IL1-BETA
IL1F2
pro-interleukin-1-beta
HGNC (Hugo) IL1B
LocusID (NCBI) 3553
Location 2q13
Location_base_pair Starts at 113587337 and ends at 113594356 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Note IL-1beta is a pro-inflamatory cytokine and is expressed by many cells including macrophage, NK cells, monocytes, and neutrophils. It belongs to the IL-1 family cluster that includes the IL-1a, and IL1-RN genes. The caspase 1 ( CASP1/ICE ) gene proteolitically activates IL-1β. This gene is involved in the proliferation, differentiation and apoptosis of cells. Inflammatory hypersensitivity has been found to be the result of IL-1β activation of cyclooxygenase-2 ( PTGS2/COX2 ). IL-1beta has also been associated with septic shock, and wound healing.

DNA/RNA

Note IL-1beta is located on Chromosome 2 at location 113,303,808-113,310,827. It is located in the middle of IL-1a and IL1-RN between 40 and 110kb from IL-1a. The pro IL-1β gene is composed of seven exons with a primary transcription product length of 7,008 nucleotides.
Description The gene spans a region of 7.5 kb and the coding part is divided into seven exons.
Transcription Transcript length: 1,498 bps; Translation length: 269 residues.

Protein

Description 269 amino acids.
Function IL-1 proteins are considered endogenous pyrogens since they are involved in inflammatory responses and also have been observed to foment prostaglandin and collagenase release from synovial cells. Additionally, IL-1 is responsible for the induction of IL-2 release, B-cell maturation/proliferation, and fibroblast growth factor activity, that stimulates thymocyte proliferation.
Homology IL-1beta shares sequence homology with IL-1a and IL1-RN. IL-1beta and IL-1a have an amino acid homology between them of approximately 25% .

Implicated in

Entity Gastric Cancer
Note Interleukin-1 beta overexpression is associated with the increased risk of both hypochlorhydria induced by H. pylori and gastric cancer (El-Omar et al., 2000). Enhancement of IL-1beta production was determined to be caused by polymorphisms in the interleukin-1 gene cluster. The pro-inflammatory properties of the IL-1 beta cytokine could explain the association with gastric cancer, also considering it is an important inhibitor of acid secretion.
  
Entity Growth of estrogen-dependent tumors
Oncogenesis In the pathogenesis of estrogen-dependent cancers, particularly, breast and ovary, the role of IL-1β is implicated in protumorigenic insults, cell proliferation, angiogenesis and cell adhesion. It appears that it is the concentration of the peptide interleukin-1 beta which determines its stimulatory or inhibitory paracrine and/or autocrine signals that regulate the growth of estrogen-dependent tumors. The IL-1β over expressing stable MCF7 cell secreting high level of IL-1β peptides shows inhibition of cell growth compared to nontransfected cells, and elevated level of p53 protein is detected in these cells (Roy et al., 2006). Stably IL-1beta transfected cells secreting moderate level of IL-1β peptides stimulate the clonal expansion of MCF7 cells. Different cellular signaling may operate in response to varying levels of IL-1β leading to genotoxic damage, cell apoptosis or cell growth .
  
Entity Tumorigenesis
Oncogenesis Il-1 beta has also been found to stimulate the local production of chemotactic factors for polymorphonuclear leukocytes (PMN's) in tumors; PMN's may play an important role in the inhibition of tumor growth.
On the other hand, other studies have found IL-1 beta to promote tumor growth. According to Vidal-Vanaclocha et al. (2000), IL-1 beta along with tumor necrosis factor-alpha (TNF-alpha), up-regulate the expression of vascular cell adhesion molecule-1 ( VCAM-1 ) on hepatic sinusoidal endothelium (HSE) in vivo which promotes cancer cell adhesion and liver metastases.
  
Entity Cardiovascular Risk, Cardiovascular Diseases
Note Increased Cardiovascular Risk, Cardiovascular Diseases
Prognosis SNPs in the interleukin-1beta gene has been reported to be associated with lower expression of basal CRP, a heritable acute-phase plasma protein, in healthy individuals. Elevated basal CRP has been associated with increased cardiovascular risk.
Additionally, an inflammatory cascade involving TNF, IL-1 beta and IL-6 has been suggested to play an important role in the pathogenesis of common postoperative problems associated with cardiac surgery involving a cardiopulmonary bypass. Increased levels of IL-6 release were associated with higher serum levels of TNF-a and IL-1β after surgery, in patients undergoing coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB).
  
Entity Liver surgery
Note Changes in tumor necrosis factor-a and interleukin-1 beta production following liver surgery.
Oncogenesis For cirrhotic patients undergoing liver surgery, changes of IL-1B and tumor necrosis factor-a levels are observed, suggesting that these two genes play an important role in the pathogenesis of postoperative liver failures. Important tissue injury and/or endotoxin, organ failures could develop and progress after stimulation of cytokine production in monocytes by factors such as insufficient blood supply (ischemia).
  
Entity Inflammation
Prognosis IL-1 beta gene might be an important neuroregulator of responses to inflammatory stressors in the central nervous system considering that overexpression of the IL-1 beta gene has been found in the CNS during systemic inflammation. IL-1a and IL-1b induction in the hypothalamus may regulate neuroendocrine functions during infection and inflammation. Wong et al (1997) propose that actions of brain IL-1 beta during systemic inflammation are an indicator of limited gene expression of cytokines in the brain to counteract IL-1 bioactivity.
  
Entity Rheumatoid Arthritis, Osteoarthritis
Prognosis IL-1 Beta activity has been linked to a TNF-alpha/cAMP pathway involved in rheumatoid arthritis. Synergistic up-regulation in IL-1 beta synthesis by TNF-alpha/cAMP has been proposed to play a role in the permanent IL-1 beta levels continuously present in chronically inflamed joints. IL-1 beta production is regulated by the TNF-alpha/cAMP pathway at the transcription level requiring a cAMP response element located between -2762 and -2755 bp in the upstream regulatory sequence of IL-1 beta.
  
Entity Periodontal Disease
Prognosis The severity of periodontal disease could be evaluated through IL-1 beta activity. Liu et al. (1996) identified IL-1beta as playing a pivotal role in the pathogenic mechanism of periodontal tissue destruction. According to the authors, clinical parameters such as gingival index (GI), probing depth (PD) and GCF flow were significantly correlated with gingival crevicular fluid (GCF) and tissue IL-1beta activity. Moreover, the degree of inflammation within periodontal disease tissue could be measured IL-1beta activity in GCF or diseased tissues based on the classification of clinical parameters.
An additional study corroborated above mentioned finding of IL-1 beta levels as a biomarker of periodontal disease. Elevated salivary levels of MMP-8 or IL-1beta or both combined, were found to significantly increase the risk of periodontal disease. Salivary levels of MMP-8 and IL-1beta could serve as biomarkers of periodontitis.
  
Entity Erosive hand osteoarthritis (OA)
Note There is a significant association between the genomic region containing the IL1B 5810 SNP and erosive hand OA in a group of US Caucasoid population (Stern et al., 2003). The IL1B 5810 AA genotype was significantly associated with the erosive hand OA subgroup (relative risk 3.8, p=0.007). The same genotype association was found significant between erosive and non-erosive hand OA subjects (relative risk 4.01, p=0.008). The IL1B 5810A allele occurs most frequently on haplotypes with the SNP alleles IL1B 1423C, IL1B 1903T, IL1B 5887C, and IL1A (-)889C.
  

External links

Nomenclature
HGNC (Hugo)IL1B   5992
Cards
AtlasIL1BID40950ch2q13
Entrez_Gene (NCBI)IL1B  3553  interleukin 1, beta
GeneCards (Weizmann)IL1B
Ensembl (Hinxton)ENSG00000125538 [Gene_View]  chr2:113587337-113594356 [Contig_View]  IL1B [Vega]
ICGC DataPortalENSG00000125538
cBioPortalIL1B
AceView (NCBI)IL1B
Genatlas (Paris)IL1B
WikiGenes3553
SOURCE (Princeton)NM_000576
Genomic and cartography
GoldenPath (UCSC)IL1B  -  2q13   chr2:113587337-113594356 -  2q14   [Description]    (hg19-Feb_2009)
EnsemblIL1B - 2q14 [CytoView]
Mapping of homologs : NCBIIL1B [Mapview]
OMIM137215   147720   
Gene and transcription
Genbank (Entrez)AB451494 AF043335 AK313983 BC008678 BT007213
RefSeq transcript (Entrez)NM_000576
RefSeq genomic (Entrez)AC_000134 NC_000002 NC_018913 NG_008851 NT_005403 NW_001838841 NW_004929304
Consensus coding sequences : CCDS (NCBI)IL1B
Cluster EST : UnigeneHs.126256 [ NCBI ]
CGAP (NCI)Hs.126256
Alternative Splicing : Fast-db (Paris)GSHG0017932
Alternative Splicing GalleryENSG00000125538
Gene ExpressionIL1B [ NCBI-GEO ]     IL1B [ SEEK ]   IL1B [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP01584 (Uniprot)
NextProtP01584  [Medical]
With graphics : InterProP01584
Splice isoforms : SwissVarP01584 (Swissvar)
Domaine pattern : Prosite (Expaxy)INTERLEUKIN_1 (PS00253)   
Domains : Interpro (EBI)Cytokine_IL1-like [organisation]   IL-1_alpha/beta [organisation]   IL-1_beta [organisation]   IL-1_CS [organisation]   IL-1_fam [organisation]   IL-1_fam/FGF_fam [organisation]   IL-1_propep [organisation]  
Related proteins : CluSTrP01584
Domain families : Pfam (Sanger)IL1 (PF00340)    IL1_propep (PF02394)   
Domain families : Pfam (NCBI)pfam00340    pfam02394   
DMDM Disease mutations3553
Blocks (Seattle)P01584
PDB (SRS)1HIB    1I1B    1IOB    1ITB    1L2H    1S0L    1T4Q    1TOO    1TP0    1TWE    1TWM    21BI    2I1B    2KH2    2NVH    31BI    3LTQ    3O4O    3POK    41BI    4DEP    4G6J    4G6M    4GAF    4GAI    4I1B    5I1B    6I1B    7I1B    9ILB   
PDB (PDBSum)1HIB    1I1B    1IOB    1ITB    1L2H    1S0L    1T4Q    1TOO    1TP0    1TWE    1TWM    21BI    2I1B    2KH2    2NVH    31BI    3LTQ    3O4O    3POK    41BI    4DEP    4G6J    4G6M    4GAF    4GAI    4I1B    5I1B    6I1B    7I1B    9ILB   
PDB (IMB)1HIB    1I1B    1IOB    1ITB    1L2H    1S0L    1T4Q    1TOO    1TP0    1TWE    1TWM    21BI    2I1B    2KH2    2NVH    31BI    3LTQ    3O4O    3POK    41BI    4DEP    4G6J    4G6M    4GAF    4GAI    4I1B    5I1B    6I1B    7I1B    9ILB   
PDB (RSDB)1HIB    1I1B    1IOB    1ITB    1L2H    1S0L    1T4Q    1TOO    1TP0    1TWE    1TWM    21BI    2I1B    2KH2    2NVH    31BI    3LTQ    3O4O    3POK    41BI    4DEP    4G6J    4G6M    4GAF    4GAI    4I1B    5I1B    6I1B    7I1B    9ILB   
Human Protein AtlasENSG00000125538 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasP01584
HPRD00985
IPIIPI00307223   IPI00916037   IPI00916174   IPI00916492   
Protein Interaction databases
DIP (DOE-UCLA)P01584
IntAct (EBI)P01584
FunCoupENSG00000125538
BioGRIDIL1B
InParanoidP01584
Interologous Interaction database P01584
IntegromeDBIL1B
STRING (EMBL)IL1B
Ontologies - Pathways
Ontology : AmiGOMAPK cascade  activation of MAPK activity  fever generation  positive regulation of protein phosphorylation  positive regulation of protein phosphorylation  positive regulation of T cell mediated immunity  cytokine activity  cytokine activity  interleukin-1 receptor binding  extracellular region  extracellular region  extracellular region  extracellular space  extracellular space  cytosol  apoptotic process  inflammatory response  inflammatory response  immune response  signal transduction  cell-cell signaling  embryo implantation  negative regulation of cell proliferation  response to carbohydrate  positive regulation vascular endothelial growth factor production  positive regulation vascular endothelial growth factor production  positive regulation of gene expression  negative regulation of glucose transport  smooth muscle adaptation  cytokine-mediated signaling pathway  protein domain specific binding  secretory granule  hyaluronan biosynthetic process  neutrophil chemotaxis  sequestering of triglyceride  positive regulation of vascular endothelial growth factor receptor signaling pathway  positive regulation of fever generation  lipopolysaccharide-mediated signaling pathway  positive regulation of prostaglandin secretion  interleukin-1 beta production  positive regulation of granulocyte macrophage colony-stimulating factor production  positive regulation of interferon-gamma production  positive regulation of interleukin-6 production  positive regulation of interleukin-8 production  positive regulation of histone phosphorylation  response to ATP  positive regulation of heterotypic cell-cell adhesion  positive regulation of heterotypic cell-cell adhesion  positive regulation of histone acetylation  ectopic germ cell programmed cell death  positive regulation of myosin light chain kinase activity  cellular response to drug  positive regulation of T cell proliferation  positive regulation of NF-kappaB import into nucleus  regulation of I-kappaB kinase/NF-kappaB signaling  positive regulation of I-kappaB kinase/NF-kappaB signaling  negative regulation of MAP kinase activity  protein kinase B signaling  positive regulation of chemokine biosynthetic process  positive regulation of interleukin-2 biosynthetic process  positive regulation of interleukin-6 biosynthetic process  positive regulation of nitric oxide biosynthetic process  positive regulation of angiogenesis  negative regulation of lipid metabolic process  positive regulation of mitosis  positive regulation of transcription, DNA-templated  positive regulation of transcription from RNA polymerase II promoter  positive regulation of JNK cascade  negative regulation of insulin receptor signaling pathway  positive regulation of protein export from nucleus  regulation of insulin secretion  negative regulation of lipid catabolic process  positive regulation of lipid catabolic process  positive regulation of membrane protein ectodomain proteolysis  positive regulation of sequence-specific DNA binding transcription factor activity  positive regulation of NF-kappaB transcription factor activity  positive regulation of cell division  positive regulation of cell adhesion molecule production  positive regulation of calcidiol 1-monooxygenase activity  negative regulation of adiponectin secretion  monocyte aggregation  cellular response to mechanical stimulus  cellular response to organic substance  cellular response to organic cyclic compound  positive regulation of monocyte chemotactic protein-1 production  extrinsic apoptotic signaling pathway in absence of ligand  negative regulation of extrinsic apoptotic signaling pathway in absence of ligand  
Ontology : EGO-EBIMAPK cascade  activation of MAPK activity  fever generation  positive regulation of protein phosphorylation  positive regulation of protein phosphorylation  positive regulation of T cell mediated immunity  cytokine activity  cytokine activity  interleukin-1 receptor binding  extracellular region  extracellular region  extracellular region  extracellular space  extracellular space  cytosol  apoptotic process  inflammatory response  inflammatory response  immune response  signal transduction  cell-cell signaling  embryo implantation  negative regulation of cell proliferation  response to carbohydrate  positive regulation vascular endothelial growth factor production  positive regulation vascular endothelial growth factor production  positive regulation of gene expression  negative regulation of glucose transport  smooth muscle adaptation  cytokine-mediated signaling pathway  protein domain specific binding  secretory granule  hyaluronan biosynthetic process  neutrophil chemotaxis  sequestering of triglyceride  positive regulation of vascular endothelial growth factor receptor signaling pathway  positive regulation of fever generation  lipopolysaccharide-mediated signaling pathway  positive regulation of prostaglandin secretion  interleukin-1 beta production  positive regulation of granulocyte macrophage colony-stimulating factor production  positive regulation of interferon-gamma production  positive regulation of interleukin-6 production  positive regulation of interleukin-8 production  positive regulation of histone phosphorylation  response to ATP  positive regulation of heterotypic cell-cell adhesion  positive regulation of heterotypic cell-cell adhesion  positive regulation of histone acetylation  ectopic germ cell programmed cell death  positive regulation of myosin light chain kinase activity  cellular response to drug  positive regulation of T cell proliferation  positive regulation of NF-kappaB import into nucleus  regulation of I-kappaB kinase/NF-kappaB signaling  positive regulation of I-kappaB kinase/NF-kappaB signaling  negative regulation of MAP kinase activity  protein kinase B signaling  positive regulation of chemokine biosynthetic process  positive regulation of interleukin-2 biosynthetic process  positive regulation of interleukin-6 biosynthetic process  positive regulation of nitric oxide biosynthetic process  positive regulation of angiogenesis  negative regulation of lipid metabolic process  positive regulation of mitosis  positive regulation of transcription, DNA-templated  positive regulation of transcription from RNA polymerase II promoter  positive regulation of JNK cascade  negative regulation of insulin receptor signaling pathway  positive regulation of protein export from nucleus  regulation of insulin secretion  negative regulation of lipid catabolic process  positive regulation of lipid catabolic process  positive regulation of membrane protein ectodomain proteolysis  positive regulation of sequence-specific DNA binding transcription factor activity  positive regulation of NF-kappaB transcription factor activity  positive regulation of cell division  positive regulation of cell adhesion molecule production  positive regulation of calcidiol 1-monooxygenase activity  negative regulation of adiponectin secretion  monocyte aggregation  cellular response to mechanical stimulus  cellular response to organic substance  cellular response to organic cyclic compound  positive regulation of monocyte chemotactic protein-1 production  extrinsic apoptotic signaling pathway in absence of ligand  negative regulation of extrinsic apoptotic signaling pathway in absence of ligand  
Pathways : BIOCARTAMsp/Ron Receptor Signaling Pathway [Genes]    NFkB activation by Nontypeable Hemophilus influenzae [Genes]    Signal transduction through IL1R [Genes]    IL 5 Signaling Pathway [Genes]   
Pathways : KEGGMAPK signaling pathway    Cytokine-cytokine receptor interaction    NF-kappa B signaling pathway    Apoptosis    Osteoclast differentiation    Toll-like receptor signaling pathway    NOD-like receptor signaling pathway    Cytosolic DNA-sensing pathway    Hematopoietic cell lineage    TNF signaling pathway    Non-alcoholic fatty liver disease (NAFLD)    Type I diabetes mellitus    Alzheimer's disease    Prion diseases    Salmonella infection    Pertussis    Legionellosis    Leishmaniasis    Chagas disease (American trypanosomiasis)    African trypanosomiasis    Malaria    Amoebiasis    Tuberculosis    Measles    Influenza A    Herpes simplex infection    Inflammatory bowel disease (IBD)    Rheumatoid arthritis    Graft-versus-host disease   
Protein Interaction DatabaseIL1B
Wikipedia pathwaysIL1B
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)IL1B
snp3D : Map Gene to Disease3553
SNP (GeneSNP Utah)IL1B
SNP : HGBaseIL1B
Genetic variants : HAPMAPIL1B
Exome VariantIL1B
1000_GenomesIL1B 
ICGC programENSG00000125538 
Somatic Mutations in Cancer : COSMICIL1B 
CONAN: Copy Number AnalysisIL1B 
Mutations and Diseases : HGMDIL1B
Mutations and Diseases : intOGenIL1B
Genomic VariantsIL1B  IL1B [DGVbeta]
dbVarIL1B
ClinVarIL1B
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM137215    147720   
MedgenIL1B
GENETestsIL1B
Disease Genetic AssociationIL1B
Huge Navigator IL1B [HugePedia]  IL1B [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneIL1B
Homology/Alignments : Family Browser (UCSC)IL1B
Phylogenetic Trees/Animal Genes : TreeFamIL1B
Chemical/Protein Interactions : CTD3553
Chemical/Pharm GKB GenePA29808
Clinical trialIL1B
Cancer Resource (Charite)ENSG00000125538
Other databases
Probes
Litterature
PubMed499 Pubmed reference(s) in Entrez
CoreMineIL1B
iHOPIL1B
OncoSearchIL1B

Bibliography

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PMID 8777275
 
Changes in tumor necrosis factor-a and interleukin-1 beta production following liver surgery on cirrhotic patients.
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Interleukin (IL) 1beta, IL-1 receptor antagonist, IL-10, and IL-13 gene expression in the central nervous system and anterior pituitary during systemic inflammation: pathophysiological implications.
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Association of erosive hand osteoarthritis with a single nucleotide polymorphism on the gene encoding interleukin-1 beta.
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Levels of IL-1 beta control stimulatory/inhibitory growth of cancer cells.
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Contributor(s)

Written05-2008Sandra Giraldo, Jesus Sanchez, Quentin Felty, Deodutta Roy
Department of Environmental and Occupational Health, Robert Stempel School of Public Health, Florida International University, Miami, FL 33199, USA

Citation

This paper should be referenced as such :
Giraldo, S ; Sanchez, J ; Felty, Q ; Roy, D
IL1B (interleukin 1, beta)
Atlas Genet Cytogenet Oncol Haematol. 2009;13(4):273-275.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/IL1BID40950ch2q13.html

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