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

Gene ID: 3576, updated on 2-Aug-2020

Summary

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 MIM:146930
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; SCYB8
Summary
The protein encoded by this gene is a member of the CXC chemokine family and is a major mediator of the inflammatory response. The encoded protein is commonly referred to as interleukin-8 (IL-8). IL-8 is secreted by mononuclear macrophages, neutrophils, eosinophils, T lymphocytes, epithelial cells, and fibroblasts. It functions as a chemotactic factor by guiding the neutrophils to the site of infection. Bacterial and viral products rapidly induce IL-8 expression. IL-8 also participates with other cytokines in the proinflammatory signaling cascade and plays a role in systemic inflammatory response syndrome (SIRS). This gene is believed to play a role in the pathogenesis of the lower respiratory tract infection bronchiolitis, a common respiratory tract disease caused by the respiratory syncytial virus (RSV). The overproduction of this proinflammatory protein is thought to cause the lung inflammation associated with csytic fibrosis. This proinflammatory protein is also suspected of playing a role in coronary artery disease and endothelial dysfunction. This protein is also secreted by tumor cells and promotes tumor migration, invasion, angiogenesis and metastasis. This chemokine is also a potent angiogenic factor. The binding of IL-8 to one of its receptors (IL-8RB/CXCR2) increases the permeability of blood vessels and increasing levels of IL-8 are positively correlated with increased severity of multiple disease outcomes (eg, sepsis). This gene and other members of the CXC chemokine gene family form a gene cluster in a region of chromosome 4q. [provided by RefSeq, May 2020]
Expression
Biased expression in bone marrow (RPKM 1065.5), appendix (RPKM 118.0) and 2 other tissues See more
Orthologs

Genomic context

See CXCL8 in Genome Data Viewer
Location:
4q13.3
Exon count:
3
Annotation release Status Assembly Chr Location
109.20200522 current GRCh38.p13 (GCF_000001405.39) 4 NC_000004.12 (73740569..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

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

HIV-1 interactions

Replication interactions

Interaction Pubs
HIV-1 ADA infection decreases production of CXCL8 (IL8), CCL2 (MCP-1), and IL6 at a basal level or after Fc receptor, completment receptor 3, or bacterial stimulation in primary human macrophages PubMed
Progressive HIV-1 infection is linked to upregulated CXCL8 (IL8), CXCR1, and PTPN11 (SHP2) expression in PBMC samples from HIV-1 infected children PubMed

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env HIV-1 CN54, JRFL, and Ada Env (gp120) upregulates IL-6, CCL2, CCL4, CXCL8, and IL-1b through TLR4 and CCR5 induction in monocyte derived macrophages and hepatic stellate cells because treatment with an anti-TLR4 antibody mitigated the response PubMed
env HIV-1 JRFL Env (gp120) upregulates IL8 in ARPE-19 cells PubMed
env HIV-1 ADA infection decreases production of CXCL8 (IL8), CCL2 (MCP-1), and IL6 at a basal level or after Fc receptor, complement receptor 3, or bacterial stimulation in primary human macrophages PubMed
env HIV-1 IIIB Env (gp120) upregulates production of TNF (TNF-a), IL-17A, CCL2 (MCP1), CCL5 (RANTES), IL6, IL10, CXCL8 (IL8), CXCL1 (GRO-a), and CCL1 (I309) in stimulated monocyte derived macrophages PubMed
env Interleukin 8 (IL-8) gene expression is enhanced in monocytes treated with HIV-1 gp120 PubMed
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
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

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
CXCR chemokine receptor binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
chemokine activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
chemokine activity IDA
Inferred from Direct Assay
more info
PubMed 
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
 
PERK-mediated unfolded protein response TAS
Traceable Author Statement
more info
 
angiogenesis TAS
Traceable Author Statement
more info
PubMed 
antimicrobial humoral immune response mediated by antimicrobial peptide IBA
Inferred from Biological aspect of Ancestor
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 IBA
Inferred from Biological aspect of Ancestor
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
PubMed 
chemotaxis TAS
Traceable Author Statement
more info
PubMed 
cytokine-mediated signaling pathway TAS
Traceable Author Statement
more info
 
embryonic digestive tract development IEP
Inferred from Expression Pattern
more info
PubMed 
immune response IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
induction of positive chemotaxis IGI
Inferred from Genetic Interaction
more info
PubMed 
inflammatory response IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
inflammatory response TAS
Traceable Author Statement
more info
PubMed 
intracellular signal transduction IDA
Inferred from Direct Assay
more info
PubMed 
leukocyte chemotaxis IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
negative regulation of G protein-coupled receptor signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of cell adhesion molecule production IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of cell proliferation TAS
Traceable Author Statement
more info
PubMed 
negative regulation of gene expression IDA
Inferred from Direct Assay
more info
PubMed 
neutrophil activation IDA
Inferred from Direct Assay
more info
PubMed 
neutrophil activation TAS
Traceable Author Statement
more info
PubMed 
neutrophil chemotaxis IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
neutrophil chemotaxis IDA
Inferred from Direct Assay
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 cellular biosynthetic process IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of gene expression 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 entry of bacterium into host cell IMP
Inferred from Mutant Phenotype
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 IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 

General protein information

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

NCBI Reference Sequences (RefSeq)

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
    5064..8211
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_000584.4NP_000575.1  interleukin-8 isoform 1 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
    ENSP00000306512.3, ENST00000307407.8
    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 ...
  2. NM_001354840.3NP_001341769.1  interleukin-8 isoform 2 precursor

    Status: REVIEWED

    Source sequence(s)
    AC112518
    Consensus CDS
    CCDS87231.1
    Related
    ENSP00000385908.1, ENST00000401931.1
    Conserved Domains (1) summary
    cd00273
    Location:3194
    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 contain an RCxC motif ...

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109.20200522

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000004.12 Reference GRCh38.p13 Primary Assembly

    Range
    73740569..73743716
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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