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FLASH GENE
Symbol IL1B contributors: mct - updated : 02-06-2019
HGNC name interleukin 1, beta
HGNC id 5992
Location 2q13      Physical location : 113.587.336 - 113.594.356
Synonym name
  • catabolin
  • preinterleukin 1 beta
  • pro-interleukin-1-beta
    • Synonym symbol(s) IL1F2, IL-1, IL1-BETA, IL-1B
    DNA
    TYPE functioning gene
    SPECIAL FEATURE component of a cluster
    STRUCTURE 7.03 kb     7 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked   status confirmed
    Map see IL1RN
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 - 1498 - 269 - 1997 9169134
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularvessel   predominantly
    Digestiveesophagus   highly
     liver   highly
     pharynx   lowly
    Lymphoid/Immunespleen   lowly
    Nervousbrain   lowly
    Respiratorylung   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  lowly
    Connectivebone  lowly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immunemacrophage
    cell lineage
    cell lines osteoblastic, gastric carcinoma predominantly
    fluid/secretion blood
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a 92 amino acids interleukin-1 propeptide domain
  • an interleukin-1 homologes domain
    • mono polymer monomer
    isoforms Precursor an 153 amino acids mature peptide (17.4 kDa)
    HOMOLOGY
    interspecies homolog to rattus Il1b (68.05 pc)
    homolog to murine Il1b (69.55 pc)
    intraspecies paralog to IL1A
    Homologene
    FAMILY
  • interleukin 1 family
  • IL-1 family
    • CATEGORY immunity/defense , signaling cytokine
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,cytosolic,granule
    basic FUNCTION
  • potential initiator and amplificator of the immune and inflammatory response
  • putatively stimulating osteoclastogenesis
  • inducing the association of TRAF6 with IRAK1, involved in the inflammatory response
  • is capable of decreasing insulin-induced glucose transport
  • involved in the negative regulation of cell proliferation
  • IL1B, released from dying cells, promotes the recruitment and retention of macrophages
  • autophagy has a potentially pivotal role to play in the induction and regulation of inflammatory responses by innate immune cells, largely driven by IL1A, IL1B and its consequential effects on IL23A secretion
  • the effects of IL1B and insulin on FOXO1 are additive, albeit independent, with respect to the distribution of FOXO1 between the nucleus and cytosol
  • MYLK is a key regulator involved in endothelial hyperpermeability, and IL1B has been shown to mediate MYLK-dependent barrier dysfunction in epithelia
  • IL1A, IL1B are important participants in the age-related exhaustion of ovarian reserve in mammalian, possibly by enhancing the expression of inflammatory genes and promoting apoptotic pathways
  • IL1A, IL1B are potent regulators of the innate immune system important for host defense but are also associated with injury and disease in the brain
  • IL1A and IL1B are key players in the innate immune system
  • IL1B promotes nuclear DNASE1 translocation in an endonuclease-inactive form
  • matricellular protein RSPO3 is a mediator of endothelial hyperpermeability that can act in synergy with the inflammatory mediator IL1B
    • CELLULAR PROCESS cell life, differentiation
    cell life, proliferation/growth
    cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS immunity/defense , inflammation
    text host response to pathogens in the NF-kappa B signaling pathway
    PATHWAY
    metabolism
    signaling signal transduction
    NF-kappa B signaling pathway
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • upregulating SLAM (signaling lymphocyte activation molecule) on mature dendritic cells
  • upregulating ADAMTS1 in stromal cells
  • IL1A stimulates cardiac myofibroblasts (CMF) to express IL1B, TNF, and IL6 via specific signaling pathways
  • IL1B induced SMAD7 negatively regulates gastrin expression
  • IL1B, IL1A both bind to the same IL1 receptor (IL1R1) and are potent proinflammatory cytokines
  • IL1B directly binds IL1A, thus identifying IL1B as a shuttle for another proinflammatory cytokine
  • a major proinflammatory cytokine, IL1B, can facilitate local progesterone metabolism in a cell type critical for maintaining uterine cervical structure via regulating expression of AKR1C1 and AKR1C2
  • IL1B regulates FOXO1 activity through a novel SMPD3-dependent pathway
  • IL1B counteracts the AKT1-mediated insulin signals by increasing the overall cellular FOXO1 content and augmenting its nuclear localization
  • NLRP3 is a key component of one of several distinct cytoplasmic multiprotein complexes (inflammasomes) that mediate the maturation of the proinflammatory cytokine IL1B by activating CASP1
  • TLR3 stimulation in keratinocytes induces a CASP4 dependent release of pro-IL1B, but further processing to active IL1B is limited
  • secretion of IL1A, IL1B, IL12B, and CCL4 occurs during gelatinase degranulation, a process controlled by STX3
  • NFKB1 may be involved in IL1B-induced activation of ADAMTS9 in human chondrocytes
  • in the presence of CASP1, CASP8 acts as a positive modulator of the NLRP3-dependent CASP1 signaling cascades that drive both IL1B production and pyroptotic death
  • PLIN2 inhibits insulin&
    • 8209;induced glucose uptake by activating NLRP3, CASP1 and IL1B, leading to a decreased IRS1 expression
  • CASP4 and caspase-5 mediate IL1A and IL1B release from human monocytes after lipopolysaccharide (LPS) stimulation
  • IL36G expression was induced by the combination of IL1B and TNF via activation of MAPKs and transcription factors, NFKB1 and JUN in colonic myofibroblasts
  • PGAM5 is a mitochondrial phosphatase that has been reported to function downstream of RIPK3 to promote necroptosis and IL1B secretion
  • IL1B regulates NOTCH1 and NOTCH4 activity in opposite directions, consistent with a selective targeting of NOTCH1 in inflamed endothelium
  • NLRC4-driven IL1B production is critical for the progression of Diabetic Nephropathy
  • new roles for CD14 and IL1B linking inflammatory dendritic cells to IL17A production in memory CD4+ T cells
  • CASP4 physically interacts with CASP1 and is believed to be a proinflammatory caspase that can induce the inflammatory form of programmed cell death (pyroptosis) and the release of mature interleukin IL1B
  • IL1B increases AMTN gene transcription in gingival epithelial cells mediated through CEBP1, CEBP2, and YY1 elements in the human AMTN gene promoter
    • cell & other
    REGULATION
    activated by after cleavage by caspase 1
    repressed by heat shock factor 1 through physical interaction with CEBPB
    Other IL1A and IL1B polyubiquitination and proteasomal degradation are central mechanisms in the regulation of intracellular IL1 levels in dendritic cells
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in multiple myeloma
    constitutional     --over  
    mRNA levels of NLRC4, NLRP12, and IL1B were significantly upregulated in Kawasaki disease (KD) patients compared to the controls
    Susceptibility
  • susceptibility factor to inflammatory bowel diseases and temporal lobe epilepsy
  • susceptibility to schizophrenia and bipolar disorder
  • to bone involvement in celiac disease
  • to Chronic kidney disease (CKD) and periodontitis (PD)
  • to diabetes
    • Variant & Polymorphism SNP , other
  • SNP 511 susceptibility to asthma exclusively in males and to schizophrenia and bipolar disorder
  • increased in febrile seizures
  • gene cluster polymorphisms are related to velocity of tooth translation
  • IL1B rs1143634(G-->A) was associated with higher blood glucose than the major allele: 5.37, 5.41, and 5.48 mmol/liter for the GG, AG, and AA genotypes, respectively
  • carriers of allele T of the interleukin-1beta gene (IL1B-511T) had a significantly lower bone mass at the total skeleton level in celiac disease
  • association of IL1B alleles with susceptibility to CKD and PD
    • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS