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FLASH GENE
Symbol IL8 contributors: mct - updated : 27-10-2016
HGNC name interleukin 8
HGNC id 6025
PROTEIN
PHYSICAL PROPERTIES acid
STRUCTURE
motifs/domains
mono polymer homomer , dimer
HOMOLOGY
Homologene
FAMILY
  • intercrine alpha (chemokine CxC) family
  • CATEGORY chaperone/stress , signaling cytokine
    SUBCELLULAR LOCALIZATION extracellular
    basic FUNCTION
  • neutrophil activating peptide 1, monocyte-derived neutrophil chemotactic factor
  • involved in the benign prostatic hyperplasia
  • functioningas a chemoattractant, and is also a potent angiogenic factor
  • potential role of IL8 to determine the fate of other inflammatory molecules, such as IL18, within the inflammatory milieu of the cystic fibrosis lung
  • chemokine with a defining CXC amino acid motif, known to possess tumorigenic and proangiogenic properties
  • signaling role for lactate in endothelial cells and they identify the lactate/NFkappaB/IL8 pathway as an important link between tumor metabolism and angiogenesis
  • essential role of IL8 signaling for the acquisition and/or maintenance of the mesenchymal and invasive features of Brachyury-overexpressing tumor cells
  • IL8 signaling plays a critical role in the epithelial-mesenchymal transition of human carcinoma cells
  • plays a neuroprotective role in the AD pathogenesis probably by modulating neuronal functions
  • protects neurons through an autocrine mechanism and that it induces the synthesis and/or release of neurotrophic factors
  • acidic histone chaperone that regulates proper CENPB binding to nucleosomes
  • IL8 is a proinflammatory chemokine important for the regulation of inflammatory and immune responses via its interaction with G-protein coupled receptors, including CXC receptor 1 (CXCR1)
  • is a key mediator of innate immune and inflammatory responses
  • IL8, a potent neutrophil-activating chemokine, exerts its function by activating the CXCR1 receptor that belongs to class A G protein-coupled receptors (GPCRs)
  • CELLULAR PROCESS cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • N- and C-terminal peptides of IL8 are ligands for IL8RA and IL8RB
  • interacting with DEFA1 (DEFA1 mainly enhanced the expression of IL8 in epithelial cells, whereas it enhanced transforming growth factor-beta and vascular endothelial growth factor expressions in lung fibroblasts)
  • CFTR function is required to suppress IL8 secretion
  • TMED1 is required for optimal IL33-induced IL8 and IL6 production
  • inhibited the non-specific binding of CENPB to nucleosomes and apparently stimulated CENPB binding to its cognate CENPB box DNA in nucleosomes
  • IL8 plays a major role in neutrophil chemotaxis caused by alveolar macrophage-derived conditioned media, and this is most effectively inhibited by dual antagonism of CXCR1 and CXCR2
  • BTC significantly increased the production of IL8 through the activation of the EGFR-PI3K/Akt-Erk signal pathway in lung cancer cells
  • IL8/CXCR1 axis is associated with the cancer stem cell (CSC)-like properties of pancratic cancer cells and prognosis in human pancreatic cancer
  • IL8 exists as monomers and dimers but monomer alone binds CXCR1 with high affinity
  • IL8 function involves binding two distinct CXCR1 sites - the N-terminal domain (Site-I) and the extracellular/transmembrane domain (Site-II)
  • extracellular acidification stimulates GPR68 mediated IL8 production in human pancreatic beta cells
  • role for CXCL1 and IL8 in CF lung disease severity and identify STAT3 as a modulating pathway
  • CNOT1 provides a platform for the recruitment of TTP and CNOT7, and is involved in TTP&
  • 8209;mediated ICAM1 and IL8 mRNA decay
  • TMPRSS11D stimulates IL8 synthesis in airway epithelial cells via F2RL1 and could help to amplify inflammation in chronic respiratory tract disease
  • cell & other
    REGULATION
    induced by Prokineticin 1 (induces CCL4, CXCL1 and IL8 in monocytes but not in macrophages and dendritic cells) (Monnier 2008)
    ENTPD1 (inhibition of ENTPD1 markedly increases IL8 production by TLR-stimulated human neutrophils)
    neurotoxins such as Abeta, as well as pro-inflammatory cytokines such as TNF, inducing CXCL8 production in neurons and Abeta and/or IL1B in glial cells
    repressed by oestradiol
    Other SNAI1 activated the expression of IL8 by direct binding to its E3/E4 E-boxes (
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in ulcerative colitis and Crohn's disease and in osteoarthritis cartilage
    tumoral     --over  
    in mesothelioma
    tumoral     --over  
    colorectal cancer (CRC), and is associated with poor prognosis
    constitutional     --over  
    significantly higher IL8 levels in Alzheimer disease brain tissue lysates as compared to those of age-matched controls
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerdigestivecolon
    important therapeutic target in colorectal cancer
    ANIMAL & CELL MODELS