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FLASH GENE
Symbol IL6 contributors: mct - updated : 03-12-2018
HGNC name interleukin 6 (interferon, beta 2)
HGNC id 6018
Location 7p15.3      Physical location : 22.766.765 - 22.771.619
Synonym name
  • B-cell differentiation factor
  • B-cell stimulatory factor 2
  • hybridoma growth factor
  • CTL differentiation factor
  • interferon beta-2
  • interleukin BSF-2
  • Synonym symbol(s) IFNB2, ILS, BSF2, HGF, HSF
    DNA
    TYPE breakpoint
    STRUCTURE 4.85 kb     5 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 - 1201 - 212 - 2009 19937696
    EXPRESSION
    Type widely
    constitutive of
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrinepancreas   highly
    Lymphoid/Immunethymus   lowly
    Nervousnervecranial nerve  moderately
    Respiratorylung   highly
    Skin/Tegumentskin   moderately
    Urinarykidney   moderately
    Visualeye   moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone  moderately
    Muscularsmoothvessel moderately
    Muscularstriatumskeletal lowly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Endocrineislet cell (alpha,beta...)
    Lymphoid/ImmuneB cell
    Respiratoryalveolar macrophage
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    conjugated GlycoP
    HOMOLOGY
    Homologene
    FAMILY
  • IL6 superfamily
  • CATEGORY signaling cytokine
    SUBCELLULAR LOCALIZATION extracellular
    text overexpressed with IL26ST in pericardium
    basic FUNCTION
  • adipokine playing an essential role in the final differentiation of B-cells into Ig-secreting cells, inducing myeloma and plasmacytoma growth, also inducing nerve cells differentiation, in hepatocytes it induces acute phase reactants
  • B cell stimulating factor 2, involved in the regulation of immune response, hematopoiesis, platelets production
  • playing a role in the aggressiveness of non Hodgkin lymphoma by stimulating MMP2 and MMP9
  • involved in protecting retinal ganglion cells from pressure-induced death
  • triggering VEGF-induced angiogenic activity through increasing VEGF release, up-regulates KDR expression and phosphorylation through activating ERK1/2 signaling, and stimulates MMP9 overexpression
  • initiates the expression of RAG1 and RAG2 in circulating B cells, and extends those in tonsil B cells
  • dual role of IL6 in inducing and terminating expression of the recombinase machinery for secondary rearrangements in mature human B cells
  • may be involved in pathophysiology of unexplained infertility
  • involved in early control of the virus, limiting activation of the adaptive immune response and preventing death of the HBV-infected hepatocyte
  • with LIF, LEP, CNTF, participate to the complex control of the reproductive function by affecting the development and function of the hypothalamus-pituitary system at different ontogenic times and anatomical sites
  • increases TJ (tight junction) permeability by stimulating the expression of CLDN2, which is required for increased CDX2 through the MEK/ERK and PI3K pathways in intestinal epithelial cells
  • implicated in the regulation of insulin secretion
  • SRC and IL6 inhibit osteoblast differentiation and integrate IGFBP5 signalling
  • IL6 produced locally by resident brain cells promotes post-stroke angiogenesis and thereby affords long-term histological and functional protection
  • mesenchymal stem cells (MSCs)-secreted IL6 and VEGFA may act as paracrine factors to sustain breast cancer cell migration
  • is now known to participate in neurogenesis (influencing both neurons and glial cells), and in the response of mature neurons and glial cells in normal conditions
  • importance of IL6 mediated stromal-epithelial cell interaction in gastric tumorigenesis. (pMID: 23593346)
  • is a T cell homeostatic cytokine that expands T cell space and can maintain the na
  • ve T cell pool
  • causes compromised tissue repair by shifting acute inflammation into a more chronic profibrotic state through induction of Th1 cell responses as a consequence of recurrent inflammation
  • IL6 is potentially increased as a result of adipose deposition and CD4(+) cell inflammation in lymphedema
  • signaling via IL6 as an important determinant of the alternative activation of macrophages and assign an unexpected homeostatic role to IL6 in limiting inflammation
  • modulates the expression of SOX2, resulting in decreased multipotency and causing primitive multipotent cells to undergo osteogenic lineage commitment
  • plays an important role in the development and progression of inflammatory responses, autoimmune diseases, and cancers
  • IL6 together with IL17A synergistically enhances the expression of survival molecules to hinder critical host defense mechanisms removing virus-infected cells
  • signalling pathways activated by IL6 have a crucial role in the regulation of CDX2 that is a key factor in the process of gastric carcinogenesis
  • is a pleiotropic cytokine with pivotal functions in the regulation of the biological responses of several target cells, including hepatocytes
  • CELLULAR PROCESS cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS immunity/defense , ossification
    text
  • bone resorption
  • acute phase reaction
  • PATHWAY
    metabolism
    signaling signal transduction
    a component CCL5-GLI2-IL6 axis in the stromal microenvironment regulating Ig secretion by malignant cells
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • markedly downregulated ENTPD2 mRNA expression
  • IL1A stimulates cardiac myofibroblasts (CMF) to express IL1B, TNF, and IL6 via specific signaling pathways
  • TNF, IL6, and leptin, which have been implicated in insulin sensitivity regulation, regulate the expression of STEAP4
  • RAB7B may play important roles in megakaryopoiesis by activating NFKB1 and promoting IL6 production
  • increased the migration and expression of MMP13 in chondrosarcoma cells
  • IL6 and IL6 receptor interaction enhances migration of chondrosarcoma through an increase in MMP13 production
  • interacting with CXCL12 (transcriptional regulation of IL6 was mediated by phosphorylation of phosphatidylinositol 3-kinase (PI3K)/Akt and activation of the activator protein AP1 component of JUN)
  • CCL5-GLI2-IL6 interaction in B cell malignancies regulates immunoglobulin secretion
  • CDH11 may be an important modulator of IL6 production by synovial fibroblasts
  • link between CSNK2A1 activity and IL6 expression
  • required for proper induction of IL6 by NFKB1
  • activates STAT5A in T cells
  • TMED1 is required for optimal IL33-induced IL8 and IL6 production
  • Il6/STAT3 modulates estrogen-induced GREB1 transcriptional activity in breast cancer cells
  • RBM8A positively regulates signals for TNF-induced IL6 production at multiple steps beyond an exon junction complex protein
  • role of KLF4 in the modulation of the inflammatory immune response via its regulation of IL6
  • BTG2 negatively regulated cancer cell growth by inhibiting IL6 expression through downregulation of STAT3 activation
  • in cancer, simultaneous upregulation of EGFR and secretion of IL6 can cooperate to desensitize the cancer cells to the actions of negative regulators, especially SOCS3
  • CD80/CD86 engagement results in DC production of the pro-inflammatory cytokine IL6, which is necessary for full T cell activation
  • DAXX selectively represses IL6 transcription through HDAC1-mediated histone deacetylation in LPS-induced macrophages
  • IL6 induced the lineage commitment and stemness loss in multipotent cells by decreasing SOX2 expression
  • CEBPB is a key transcription factor, which can positively regulate the expression of TMUB1 during liver cell proliferation through a possible association with IL6
  • key role for SENP1 in IL6 induced proliferation and survival of multiple myeloma cells
  • IL6 is a master regulator of IL21 in effector CD8+ T cells
  • promotes proinflammatory IL6 expression and extracellular matrix remodeling in visceral adipose stem cells
  • IFNA1 markedly induced IL6 expression in hepatocytes, especially in HBV replicating hepatocytes
  • cell & other
    REGULATION
    induced by TLR/Il1 (reqiring MAIL)
    Other regulated by ATM (ATM was essential for IL6 secretion during oncogene-induced senescence and by damaged cells that bypass senescence)
    EDN1 induces mRNA and protein secretion of CCL2 and IL6, forming an autocrine signaling pathway that stimulates collagen accumulation in the extracellular matrix
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in inflammatory bowel diseases
    tumoral     --over  
    in inflammatory breast cancer
    constitutional     --over  
    in midlife predicts cognitive decline
    constitutional     --over  
    in primary and secondary models of lymphedema
    constitutional     --over  
    increased in the plasma of patients with cerebral arteriovenous malformation
    constitutional     --over  
    in hepatitis B patients
    Susceptibility
  • susceptibility in carotid artery atherosclerosis and osteopenia
  • to Kaposi sarcoma
  • to juvenile rheumatoid arthritis (OMIM: 604302)
  • to cerebral palsy in term and near-term infants (CP)
  • to type 2 diabetes
  • to osteoporosis (bone mineral density)
  • elevated IL-6 levels are strongly associated with future cardiac events and mortality in a population with stable coronary artery disease during a long-term follow-up
  • to sporadic Alzheimer's disease
  • Variant & Polymorphism other
  • in juvenile rheumatoid arthritis
  • G/C promoter polymorphism in NIDDM (in native Americans and Caucasians)
  • C174G associated with bone loss in postmenopausal women
  • -572C/G polymorphism of IL6 gene promoter region is associated with AD, and G allele is an independent protective factor for AD
  • functional polymorphism in the IL6 gene is a risk factor for CP among term and near-term infants
  • Candidate gene
    Marker
  • cerebrospinal fluid (CSF) IL6 may help to differentiate multiple sclerosis (MS) from other inflammatory neurological diseases (OIND)
  • Therapy target
    SystemTypeDisorderPubmed
    immunologyautoimmunearticular
    antibodies specific as therapeutic targets in rheumatoid arthritis
    immunologyinfectiousaquired
    therapeutic neutralization of IL6 for treatment of certain diseases may represent a risk if the patient is HBV-infected
    diabete  
    use of therapeutic strategies aimed at antagonizing CCL2 or IL6 signaling in diabetic kidney injury
    immunologyautoimmunearticular
    potential therapeutic target in rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA)
    ANIMAL & CELL MODELS