Similarities and differences between the responses induced in human phagocytes through activation of the medium chain fatty acid receptor GPR84 and the short chain fatty acid receptor FFA2R.

Biochimica Et Biophysica Acta. Molecular Cell Research
Martina SundqvistHuamei Forsman

Abstract

GPR84 is a recently de-orphanized member of the G-protein coupled receptor (GPCR) family recognizing medium chain fatty acids, and has been suggested to play important roles in inflammation. Due to the lack of potent and selective GPR84 ligands, the basic knowledge related to GPR84 functions is very limited. In this study, we have characterized the GPR84 activation profile and regulation mechanism in human phagocytes, using two recently developed small molecules that specifically target GPR84 agonistically (ZQ16) and antagonistically (GLPG1205), respectively. Compared to our earlier characterization of the short chain fatty acid receptor FFA2R which is functionally expressed in neutrophils but not in monocytes, GPR84 is expressed in both cell types and in monocyte-derived macrophages. In neutrophils, the GPR84 agonist had an activation profile very similar to that of FFA2R. The GPR84-mediated superoxide release was low in naïve cells, but the response could be significantly primed by TNFα and by the actin cytoskeleton disrupting agent Latrunculin A. Similar to that of FFA2R, a desensitization mechanism bypassing the actin cytoskeleton was utilized by GPR84. All ZQ16-mediated cellular responses were sensitive to GLPG1205, confir...Continue Reading

Citations

Feb 28, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Simon LindClaes Dahlgren
Sep 2, 2020·British Journal of Pharmacology·Sara MarsangoGraeme Milligan
Oct 2, 2020·DNA and Cell Biology·Vincent B LuscombeDavid R Greaves
Feb 14, 2019·Scientific Reports·Sarah J ManciniGraeme Milligan
Dec 11, 2019·Nutrients·Urszula RadzikowskaMilena Sokolowska
Sep 12, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Martina SundqvistHuamei Forsman
Dec 19, 2020·Cell Death and Differentiation·Giulia CerratoGuido Kroemer
Apr 17, 2020·ACS Pharmacology & Translational Science·Claes DahlgrenHuamei Forsman
Mar 7, 2021·International Journal of Molecular Sciences·Paula O CooperBrett A Shook
Jun 18, 2021·International Journal of Inflammation·Vadim GenkelIgor Shaposhnik

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