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FLASH GENE
Symbol IL8 contributors: mct - updated : 27-10-2018
HGNC name interleukin 8
HGNC id 6025
Location 4q13.3      Physical location : 74.606.274 - 74.609.431
Synonym name
  • chemokine (C-X-C motif) ligand 8
  • neutrophils activating peptide 1
  • emoctakin
  • granulocyte chemotactic protein 1
  • monocyte-derived neutrophil-activating peptide
  • beta-thromboglobulin-like protein
  • small inducible cytokine subfamily B, member 8
    • Synonym symbol(s) K60, LECT, LUCT, CXCL8, GCP-1, GCP1, LYNAP, IL-8, MDNCF, MONAP, NAP-1, NAP1, SCYB8, TSG-1, AMCF-I, b-ENAP, NAF, 3-10C
    DNA
    TYPE functioning gene
    SPECIAL FEATURE component of a cluster
    STRUCTURE 3.16 kb     4 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked Y status confirmed
    Map cen - IL8 - CXCL1 / PPBP / PF4 - CXCL5 / CXCL6 - CXCL2 / CXCL3 - CXCL11 - CXCL10 - CXCL9 - qter
    Authors O'Donovan et al. (99)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 - 1666 - 99 - - 9828130
    EXPRESSION
    Type widely
    constitutive of
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   lowly
    Endocrinepancreas   highly
    Reproductivemale systemprostate  lowly
    Respiratorylung   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoietic   highly
    Epithelialbarrier/liningepidermis  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Endocrineislet cell (alpha,beta...)
    Reproductiveepithelial cell
    cell lineage
    cell lines
    fluid/secretion blood
    at STAGE
    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)
  • IL8, IL6, IL5 might likely play central roles in cytokine storms associated with COVID-19
    • 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