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    CXCL8 C-X-C motif chemokine ligand 8 [ Homo sapiens (human) ]

    Gene ID: 3576, updated on 28-Aug-2016
    Official Symbol
    CXCL8provided by HGNC
    Official Full Name
    C-X-C motif chemokine ligand 8provided by HGNC
    Primary source
    HGNC:HGNC:6025
    See related
    Ensembl:ENSG00000169429 HPRD:00909; MIM:146930; Vega:OTTHUMG00000151316
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    IL8; NAF; GCP1; LECT; LUCT; NAP1; GCP-1; LYNAP; MDNCF; MONAP; NAP-1
    Summary
    The protein encoded by this gene is a member of the CXC chemokine family. This chemokine is one of the major mediators of the inflammatory response. This chemokine is secreted by several cell types. It functions as a chemoattractant, and is also a potent angiogenic factor. This gene is believed to play a role in the pathogenesis of bronchiolitis, a common respiratory tract disease caused by viral infection. This gene and other ten members of the CXC chemokine gene family form a chemokine gene cluster in a region mapped to chromosome 4q. [provided by RefSeq, Jul 2008]
    Orthologs
    Location:
    4q13-q21
    Exon count:
    4
    Annotation release Status Assembly Chr Location
    108 current GRCh38.p7 (GCF_000001405.33) 4 NC_000004.12 (73740506..73743716)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (74606223..74609433)

    Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene Ras association domain family member 6 Neighboring gene uncharacterized LOC105377272 Neighboring gene C-X-C motif chemokine ligand 6 Neighboring gene pro-platelet basic protein pseudogene 1

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env Curcumin, a potent and safe anti-inflammatory compound, inhibits HIV-1 gp120-mediated upregulation of the proinflammatory cytokines TNF-alpha and IL-6, and the chemokines IL-8, RANTES, and IP-10 in primary human genital epithelial cells PubMed
    env HIV-1 gp120 upregulates the expression of interleukin 8 (IL8) in human B cells PubMed
    env HIV-1 gp120 upregulates the expression of IL-6 and IL-8 via the p38 signaling pathway and the PI3K/Akt signaling pathway in astrocytes PubMed
    env The binding of soluble HIV-1 gp120 to TLR2 or TLR4 results in upregulation of the TNF-alpha and IL-8 production through NF-kappaB activation PubMed
    env HIV-1 gp120-mediated increases in IL-8 production in astrocytes are mediated through the NF-KappaB pathway PubMed
    env In endometrial epithelium-derived cells, gp120 from CCR5-tropic HIV-1 increases the release of monocytes/chemokines-attracting chemokines (IL-8 and GRO) and proinflammatory cytokines (TNF-beta and IL-1alpha) PubMed
    env Interleukin 8 (IL-8) gene expression is enhanced in monocytes treated with HIV-1 gp120 PubMed
    Envelope transmembrane glycoprotein gp41 env The binding of soluble TLR2 to HIV-1 MA, CA, or gp41 inhibits the nuclear translocation of NFKB p65 subunit and downregulates CXCL8 (IL-8) and CCR5 expression, leading to inhibition of HIV-1 infection in cells PubMed
    env Evidence suggests HIV CA (p24) binds TLR2 and blocks activation by HIV MA (p17) and/or gp41 BUT DOES NOT block activation via Pam3CSK4 suggesting that HIV manipulates innate immune signaling through a TLR2-dependent mechanism PubMed
    env Exposure of TZM-bl 2 cells to CA (p24) for 1h prior to HIV gp41 decreases CXCL8 (IL-8) production yet has little to no effect on the inhibition of Pam3CSK4 (a synthetic bacterial TLR2/1 ligand) production of CXCL8 (IL-8) PubMed
    env Exposure of human T cells to HIV gp41 increases extracellular CXCL8 (IL-8) levels but to a lesser extent than CA (p24) and gp41 PubMed
    env A synthetic peptide corresponding to the immunosuppressive domain (amino acids 574-592) of HIV-1 gp41 inhibits activation of PBMCs and upregulates the expression of IL-8 in peptide-treated PBMCs PubMed
    env The interaction between HIV-1 gp41 fusion peptide and lymphocyte membrane is blocked by interleukin-8 and abolished by pre-treating the cells with heparin sulfate (HS) PubMed
    Nef nef HIV-1 Nef induces IL6 and CXCL8 (IL8) expression in a PIK3-PKC dependent, AKT independent manner PubMed
    nef HIV-1 Nef induces IL6 and IL8 expression through the NF-kappaB pathway PubMed
    nef HIV-1 Nef treatment induces IL6 and IL8 production in SVGA cells and primary human fetal astrocytes PubMed
    nef HIV-1 Tat and Nef combination treatment induces release of both IL-6 and IL-8 in human mesenchymal stem cells PubMed
    nef HIV-1 Nef expression by immature human and macaque dendritic cells (DCs) upregulates IL-6, IL-12, TNF-alpha, CXCL8, CCL3, and CCL4 release, but without upregulating co-stimulatory and other molecules characteristic of mature DCs PubMed
    Pr55(Gag) gag MVA-gag induces a significant release of cytokines such as IL-2R, IL-6, IL-8, TNF-alpha, IFN-gamma, MCP-1, MIP-1alpha, MIP-1beta, and RANTES by the infected monocyte-derived dendritic cells in comparison with uninfected cells PubMed
    Tat tat HIV-1 Tat upregulates CXCL8 mRNA and protein expression in CRT-MG human astroglioma cells PubMed
    tat HIV-1 Tat upregulates (CXCL8) IL8 protein expression in human monocytes and monocyte-derived dendritic cells in a TLR4-CD14-MD2 dependent manner PubMed
    tat HIV-1 Tat and Nef combination treatment induces release of both IL-6 and IL-8 in human mesenchymal stem cells PubMed
    tat HIV-1 Tat-induced upregulation of IL-8 in a time-dependent manner involves NF-kappaB and AP-1 transcription factors, activation of the p38 MAPK beta subunit, and PI3K/Akt pathway in astrocytes PubMed
    tat HIV-1 Tat upregulates IL-8 expression in astrocytes, monocytes, monocyte derived macrophages, Jurkat T-cells, HeLa cells, and human brain endothelial cells, an effect that likely contributes to the immune dysregulation observed during HIV-1 infection PubMed
    tat HIV-1 Tat downregulates the expression of adiponectin protein and upregulates the expression of IL-6, IL-8, and MCP-1 proteins in human SGBS preadipocytes PubMed
    tat HIV-1 Tat protein upregulates expression of IL-6 and IL-8 in human breast cancer cells by an NF-kappaB-dependent pathway PubMed
    tat HIV-1 Tat upregulates IL-8 and VEGF production and release from polymorphonuclear leukocytes (PMNL), indicating that PMNL recruitment by Tat is linked to angiogenesis PubMed
    tat HIV-1 Tat upregulation of IL-8 is linked to the cell cycle and involves NF-kappa B, RelA, c-rel, and CREB-binding protein PubMed
    tat Upregulation of IL-8 by HIV-1 Tat is implicated in the pathogenesis of Kaposi's sarcoma PubMed
    tat HIV-1 Tat downregulates IL-8 expression in the Raji B-cell line, however in the presence of PMA+PHA Tat induced IL-8 expression PubMed
    tat Upregulation of IL-8 by HIV-1 Tat in astrocytes is inhibited by the MEK1/2 inhibitor UO126, indicating a role for MEK1/2 in Tat-mediated chemokine induction PubMed
    Vpr vpr Treatment of human primary astrocytes with HIV-1 Vpr upregulates secretion of IL6, CXCL8 (IL8), MCP-1, and MIF and downregulates secretion of serpin E1, a serine proteinase inhibitor (known as PAI-1) PubMed
    vpr HIV-1 Vpr downregulates the expression of IL8 in human monocyte-derived dendritic cells PubMed
    vpr HIV-1 Vpr induced upregulation of CXCL8 (IL8) involves PI3K/Akt mediated activation of NFKB1 (NF-kappa-B) in astrocytes PubMed
    vpr HIV-1 Vpr-mediated upregulation of CXCL8 (IL8) involves NFKB1 (NF-kappa-B) PubMed
    vpr HIV-1 Vpr enhances the secretion of CXCL8 (IL8) from human fetal astrocytes PubMed
    vpr HIV-1 Vpr upregulates the expression of CXCL8 (IL8) mRNA in human fetal astrocytes PubMed
    vpr HIV-1 Vpr upregulates the expression fo CXCL8 (IL8) mRNA in SVGA in a dose-dependent manner PubMed
    vpr HIV-1 Vpr upregulates the expression of CXCL8 (IL8) mRNA in SVGA astrocytes in a time dependent fashion PubMed
    vpr HIV-1 Vpr enhances the secretion of CXCL8 (IL8) from SVGA astrocytes in a time dependent fashion PubMed
    vpr HIV-1 involves the JUN (AP-1) transcription factor in the induction of CXCL8 (IL8) in astrocytes PubMed
    vpr HIV-1 Vpr involves the CEBPD (C/EBP-delta) transcription factor in the induction of CXCL8 (IL8) in astrocytes PubMed
    vpr Vpr-mediated upregulation of CXCL8 (IL8) involves MAPK8 (JnK-MAPK) in astrocytes PubMed
    vpr Vpr-mediated upregulation of CXCL8 (IL8) in astrocytes involves p38-MAPK11 (beta isoform of p38-MAPK) PubMed
    vpr HIV-1 Vpr regulates interleukin 8 (CXCL8 (IL8)) expression, with reports showing both up- and downregulation of CXCL8 (IL8) PubMed
    capsid gag CXCL8-induced upregulation of HIV-1 p24 levels and 2-LTR circles is inhibited by CXCR1 or CXCR2 neutralization in HIV-1-infected monocytes-derived macrophages PubMed
    gag The binding of soluble TLR2 to HIV-1 MA, CA, or gp41 inhibits the nuclear translocation of NFKB p65 subunit and downregulates CXCL8 (IL-8) and CCR5 expression, leading to inhibition of HIV-1 infection in cells PubMed
    gag Treatment with chemokine CXCL8 significantly upregulates HIV-1 CA (p24) levels in supernatants of both HIV-1-infected monocytes-derived macrophages as well as microglia in a dose-dependent manner PubMed
    gag Evidence suggests HIV CA (p24) binds TLR2 and blocks activation by HIV MA (p17) and/or gp41 BUT DOES NOT block activation via Pam3CSK4 suggesting that HIV manipulates innate immune signaling through a TLR2-dependent mechanism PubMed
    gag Simultaneous exposure of TZM-bl2 cells with HIV CA(p24) and MA (p17) decreases MA (p17)- induced production of CXCL8 (IL-8) in a dose-dependent manner PubMed
    gag Exposure of TZM-bl 2 cells to CA(p24) for 1h prior to HIV gp41 or MA (p17) decreases CXCL8 (IL-8) production yet has little to no effect on the inhibition of Pam3CSK4 (a synthetic bacterial TLR2/1 ligand) production of CXCL8 (IL-8) PubMed
    gag Exposure of human T cells to HIV CA (p24) increases extracellular CXCL8 (IL-8) levels in a dose dependent manner and to a greater extent than gp41 but to a lesser extent than MA (p17) exposures. PubMed
    gag PLA-p24-loaded human monocyte-derived dendritic cells enhance the secretion of MIP-1beta, IL-6, IL-8, and TNF-alpha in comparison with PLA-loaded cells alone PubMed
    integrase gag-pol The formation of 2-long terminal repeat circles, a measure of viral genome integration, is higher in CXCL8-treated, HIV-1-infected monocytes-derived macrophages and microglia, suggesting the interaction between HIV-1 IN and CXCL8 PubMed
    gag-pol IL-8 decreases HIV-1 reverse transcription and viral integration during the early infection, suggesting the interaction between HIV-1 IN and IL-8 PubMed
    matrix gag Evidence suggests HIV CA (p24) binds TLR2 and blocks activation by HIV MA (p17) and/or gp41 BUT DOES NOT block activation via Pam3CSK4 suggesting that HIV manipulates innate immune signaling through a TLR2-dependent mechanism PubMed
    gag Simultaneous exposure of TZM-bl2 cells with HIV CA(p24) and MA (p17) decreases MA (p17)- induced production of CXCL8 (IL-8) in a dose-dependent manner PubMed
    gag Exposure of TZM-bl 2 cells to CA(p24) for 1h prior to HIV MA(p17) decreases CXCL8 (IL-8) production yet has little to no effect on the inhibition of Pam3CSK4 (a synthetic bacterial TLR2/1 ligand) production of CXCL8 (IL-8) PubMed
    gag Exposure of human T cells to HIV MA (p17) increases extracellular CXCL8 (IL-8) levels in a dose dependent manner and to a greater extent than CA (p24) and gp41. PubMed
    gag The binding of soluble TLR2 to HIV-1 MA, CA, or gp41 inhibits the nuclear translocation of NFKB p65 subunit and downregulates IL-8 and CCR5 expression, leading to inhibition of HIV-1 infection in cells PubMed
    gag Surface plasmon resonance analysis reveals that HIV-1 p17 binds IL-8 PubMed
    nucleocapsid gag HIV-1 NC upregulates IL8 in HEK 293T cells PubMed
    reverse transcriptase gag-pol IL-8 decreases HIV-1 reverse transcription and viral integration during the early infection, suggesting the interaction between HIV-1 RT and IL-8 PubMed

    Go to the HIV-1, Human Interaction Database

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      Syndecan-3-mediated signaling events, organism-specific biosystem
      Syndecan-3-mediated signaling events
    • TSLP Signaling Pathway, organism-specific biosystem (from WikiPathways)
      TSLP Signaling Pathway, organism-specific biosystemThymic stromal lymphopoietin (TSLP) is a type I cytokine member of interleukin-2 cytokine family. TSLP signals through interleukin-7 receptor a chain (IL-7Ra) and the TSLP receptor subunit (TSLPR), h...
    • Toll-like receptor signaling pathway, organism-specific biosystem (from KEGG)
      Toll-like receptor signaling pathway, organism-specific biosystemSpecific families of pattern recognition receptors are responsible for detecting microbial pathogens and generating innate immune responses. Toll-like receptors (TLRs) are membrane-bound receptors id...
    • Toll-like receptor signaling pathway, organism-specific biosystem (from WikiPathways)
      Toll-like receptor signaling pathway, organism-specific biosystemSpecific families of pattern recognition receptors are responsible for detecting microbial pathogens and generating innate immune responses. Toll-like receptors (TLRs) are membrane-bound receptors id...
    • Toll-like receptor signaling pathway, conserved biosystem (from KEGG)
      Toll-like receptor signaling pathway, conserved biosystemSpecific families of pattern recognition receptors are responsible for detecting microbial pathogens and generating innate immune responses. Toll-like receptors (TLRs) are membrane-bound receptors id...
    • Transcriptional misregulation in cancer, organism-specific biosystem (from KEGG)
      Transcriptional misregulation in cancer, organism-specific biosystem
      Transcriptional misregulation in cancer
    • Transcriptional misregulation in cancer, conserved biosystem (from KEGG)
      Transcriptional misregulation in cancer, conserved biosystem
      Transcriptional misregulation in cancer
    • Unfolded Protein Response (UPR), organism-specific biosystem (from REACTOME)
      Unfolded Protein Response (UPR), organism-specific biosystemThe Unfolded Protein Response (UPR) is a regulatory system that protects the Endoplasmic Reticulum (ER) from overload. The UPR is provoked by the accumulation of improperly folded protein in the ER d...
    • Validated transcriptional targets of AP1 family members Fra1 and Fra2, organism-specific biosystem (from Pathway Interaction Database)
      Validated transcriptional targets of AP1 family members Fra1 and Fra2, organism-specific biosystem
      Validated transcriptional targets of AP1 family members Fra1 and Fra2
    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    chemokine activity TAS
    Traceable Author Statement
    more info
    PubMed 
    interleukin-8 receptor binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    Process Evidence Code Pubs
    G-protein coupled receptor signaling pathway TAS
    Traceable Author Statement
    more info
    PubMed 
    PERK-mediated unfolded protein response TAS
    Traceable Author Statement
    more info
     
    angiogenesis TAS
    Traceable Author Statement
    more info
    PubMed 
    calcium-mediated signaling TAS
    Traceable Author Statement
    more info
    PubMed 
    cell cycle arrest IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cellular response to fibroblast growth factor stimulus IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    cellular response to interleukin-1 IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    cellular response to lipopolysaccharide IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cellular response to tumor necrosis factor IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    chemokine-mediated signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    chemotaxis TAS
    Traceable Author Statement
    more info
    PubMed 
    embryonic digestive tract development IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    immune response IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    induction of positive chemotaxis IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    inflammatory response TAS
    Traceable Author Statement
    more info
    PubMed 
    intracellular signal transduction IDA
    Inferred from Direct Assay
    more info
    PubMed 
    movement of cell or subcellular component TAS
    Traceable Author Statement
    more info
    PubMed 
    negative regulation of G-protein coupled receptor protein signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    negative regulation of cell proliferation TAS
    Traceable Author Statement
    more info
    PubMed 
    neutrophil activation TAS
    Traceable Author Statement
    more info
    PubMed 
    neutrophil chemotaxis IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    positive regulation of angiogenesis IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of neutrophil chemotaxis TAS
    Traceable Author Statement
    more info
    PubMed 
    receptor internalization IDA
    Inferred from Direct Assay
    more info
    PubMed 
    regulation of cell adhesion IDA
    Inferred from Direct Assay
    more info
    PubMed 
    regulation of single stranded viral RNA replication via double stranded DNA intermediate IDA
    Inferred from Direct Assay
    more info
    PubMed 
    response to endoplasmic reticulum stress IDA
    Inferred from Direct Assay
    more info
    PubMed 
    response to molecule of bacterial origin IDA
    Inferred from Direct Assay
    more info
    PubMed 
    signal transduction TAS
    Traceable Author Statement
    more info
    PubMed 
    Component Evidence Code Pubs
    extracellular region TAS
    Traceable Author Statement
    more info
     
    extracellular space IEA
    Inferred from Electronic Annotation
    more info
     
    intracellular IEA
    Inferred from Electronic Annotation
    more info
     
    Preferred Names
    interleukin-8
    Names
    T-cell chemotactic factor
    alveolar macrophage chemotactic factor I
    beta endothelial cell-derived neutrophil activating peptide
    beta-thromboglobulin-like protein
    chemokine (C-X-C motif) ligand 8
    emoctakin
    granulocyte chemotactic protein 1
    interleukin 8
    lung giant cell carcinoma-derived chemotactic protein
    lymphocyte derived neutrophil activating peptide
    monocyte-derived neutrophil chemotactic factor
    monocyte-derived neutrophil-activating peptide
    neutrophil-activating peptide 1
    small inducible cytokine subfamily B, member 8
    tumor necrosis factor-induced gene 1

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_029889.1 RefSeqGene

      Range
      5001..8211
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000584.3NP_000575.1  interleukin-8 precursor

      See identical proteins and their annotated locations for NP_000575.1

      Status: REVIEWED

      Source sequence(s)
      BC013615, BG497712
      Consensus CDS
      CCDS34005.1
      UniProtKB/Swiss-Prot
      P10145
      UniProtKB/TrEMBL
      A0A024RDA5
      Related
      ENSP00000306512, OTTHUMP00000199824, ENST00000307407, OTTHUMT00000322211
      Conserved Domains (1) summary
      cd00273
      Location:3194
      Chemokine_CXC; Chemokine_CXC: 1 of 4 subgroup designations based on the arrangement of the two N-terminal cysteine residues; includes a number of secreted growth factors and interferons involved in mitogenic, chemotactic, and inflammatory activity; many members ...

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 108 details...

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p7 Primary Assembly

    Genomic

    1. NC_000004.12 Reference GRCh38.p7 Primary Assembly

      Range
      73740506..73743716
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate CHM1_1.1

    Genomic

    1. NC_018915.2 Alternate CHM1_1.1

      Range
      74642243..74645454
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)