Interleukin 8 receptor, alpha is a
chemokine receptor. This name and the corresponding
gene symbol IL8RA have been replaced by the
HGNC approved name C-X-C motif chemokine receptor 1 and the approved symbol CXCR1. It has also been designated as CD181 (
cluster of differentiation 181). The
IUPHAR Committee on Receptor Nomenclature and Drug Classification use the HGNC recommended name, CXCR1.
Function
The protein encoded by this gene is a member of the
G-protein-coupled receptor family. This protein is a receptor for
interleukin 8 (IL8). It binds to IL8 with high affinity, and transduces the signal through a G-protein-activated second messenger system. Knockout studies in mice suggested that this protein inhibits embryonic
oligodendrocyte precursor migration in developing spinal cord.
IL8RA,
IL8RB, which encodes another high affinity IL8 receptor, and IL8RBP, a pseudogene of IL8RB, form a gene cluster in a region mapped to chromosome 2q33-q36.[5] Stimulation of CXCR1 in
neutrophils by its primary ligand,
Interleukin 8, leads to neutrophil
chemotaxis and activation.[6]
Clinical significance
Blocking CXCR1 (e.g., with
repertaxin[7]) inhibits some human breast cancer stem cells (in vitro and in mice).[8]
In malignant melanoma expression of CXCR1 at the cell surface is present, independent of the cancers stage. It is thought to have a role in the cell growth and angiogenesis required for tumour survival. In this way it has been identified as a potential therapeutic target.[9]
CXCR1 can be cleaved and inactivated by Neutrophil Derived Serine Proteases (NSPs), leading to neutrophil dysfunction and impaired bacterial killing in
cystic fibrosis lung disease.[10]
^Casilli F, Bianchini A, Gloaguen I, Biordi L, Alesse E, Festuccia C, Cavalieri B, Strippoli R, Cervellera MN, Di Bitondo R, Ferretti E, Mainiero F, Bizzarri C, Colotta F, Bertini R (February 2005). "Inhibition of interleukin-8 (CXCL8/IL-8) responses by repertaxin, a new inhibitor of the chemokine receptors CXCR1 and CXCR2". Biochem. Pharmacol. 69 (3): 385–94.
doi:
10.1016/j.bcp.2004.10.007.
PMID15652230.
Morris SW, Nelson N, Valentine MB, Shapiro DN, Look AT, Kozlosky CJ, Beckmann MP, Cerretti DP (1992). "Assignment of the genes encoding human interleukin-8 receptor types 1 and 2 and an interleukin-8 receptor pseudogene to chromosome 2q35". Genomics. 14 (3): 685–91.
doi:
10.1016/S0888-7543(05)80169-7.
PMID1427896.
Schnitzel W, Monschein U, Besemer J (1994). "Monomer-dimer equilibria of interleukin-8 and neutrophil-activating peptide 2. Evidence for IL-8 binding as a dimer and oligomer to IL-8 receptor B". J. Leukoc. Biol. 55 (6): 763–70.
doi:
10.1002/jlb.55.6.763.
PMID8195702.
S2CID5948202.
Cerretti DP, Kozlosky CJ, Vanden Bos T, Nelson N, Gearing DP, Beckmann MP (1993). "Molecular characterization of receptors for human interleukin-8, GRO/melanoma growth-stimulatory activity and neutrophil activating peptide-2". Mol. Immunol. 30 (4): 359–67.
doi:
10.1016/0161-5890(93)90065-J.
PMID8384312.
Mollereau C, Muscatelli F, Mattei MG, Vassart G, Parmentier M (1993). "The high-affinity interleukin 8 receptor gene (IL8RA) maps to the 2q33-q36 region of the human genome: cloning of a pseudogene (IL8RBP) for the low-affinity receptor". Genomics. 16 (1): 248–51.
doi:
10.1006/geno.1993.1167.
PMID8486366.
"Chemokine Receptors: CXCR1". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived from
the original on 2016-03-03. Retrieved 2008-12-03.