HGNC Approved Gene Symbol: GPR18
Cytogenetic location: 13q32.3 Genomic coordinates (GRCh38): 13:99,254,739-99,258,379 (from NCBI)
Resolution of acute inflammation, which is essential for host defense and return to homeostasis, is governed by class switching of lipid mediators from production of proinflammatory prostaglandins and leukotrienes to biosynthesis of antiinflammatory and proresolving mediators. GPR18 is a cell surface G protein-coupled receptor (GPCR) for resolvin D2 (RvD2), a potent docosahexaenoic acid-derived resolution-phase mediator (Chiang et al., 2015)
Gantz et al. (1997) used low-stringency PCR to isolate a fragment of a novel putative GPCR from human colon cancer cell line RNA. They cloned the corresponding genomic DNA from a human phage library and reported that the gene encodes a 331-amino acid polypeptide. The protein has 7 putative transmembrane domains, but it shares less than 34% amino acid similarity with other GPCRs. Northern blot analysis showed that the GPR18 transcript was most abundant in human testis and spleen; transcripts were also detected in several other tissues associated with the immune system.
Using flow cytometry, Chiang et al. (2015) showed that GPR18 was expressed on human leukocytes, including polymorphonuclear (PMN) cells, monocytes, and macrophages.
Gantz et al. (1997) stated that the human GPR18 gene is probably intronless.
Gantz et al. (1997) used fluorescence in situ hybridization to map the GPR18 gene to human chromosome 13q32. They noted that this localization is in agreement with a previous mapping of Gpr18 to mouse chromosome 14.
By screening human GPCRs to identify a receptor for RvD2, Chiang et al. (2015) identified GPR18. In human macrophages, RvD2-stimulated intracellular cAMP was dependent on GPR18. RvD2-stimulated phagocytosis of bacteria and PMN-cell efferocytosis were enhanced by GPR18 overexpression and significantly reduced by GPR18 knockdown with short hairpin RNA. Radiolabeled RvD2 bound directly to recombinant human GPR18 with an affinity in the RvD2 bioactive concentration range. Chiang et al. (2015) concluded that a RvD2-GPR18 resolution axis stimulates phagocyte functions to control bacterial infections and promote organ protection.
By infecting mice with Escherichia coli or Staphylococcus aureus, Chiang et al. (2015) showed that RvD2 limited PMN-cell infiltration, enhanced phagocyte clearance of bacteria, and accelerated resolution. Mice deficient in Gpr18 lost these activities.
Chiang, N., Dalli, J., Colas, R. A., Serhan, C. N. Identification of resolvin D2 receptor mediating resolution of infections and organ protection. J. Exp. Med. 212: 1203-1217, 2015. [PubMed: 26195725] [Full Text: https://doi.org/10.1084/jem.20150225]
Gantz, I., Muraoka, A., Yang, Y.-K., Samuelson, L. C., Zimmerman, E. M., Cook, H., Yamada, T. Cloning and chromosomal localization of a gene (GPR18) encoding a novel seven transmembrane receptor highly expressed in spleen and testis. Genomics 42: 462-466, 1997. [PubMed: 9205118] [Full Text: https://doi.org/10.1006/geno.1997.4752]