RGS13 restricts G‐protein‐coupled receptor‐induced responses in mast cells

Abstract

Mast cell degranulation and release of vasoactive mediators and cytokines promotes allergic reactions and innate immunity. Regulator of G protein signaling (RGS) proteins attenuate G‐protein‐coupled receptor (GPCR)‐evoked signaling pathways by binding heterotrimeric G protein alpha subunits and acting as GTPase accelerating proteins (GAPs). Several RGS proteins were expressed in mast cells including RGS13. We found previously that RGS13 suppressed IgE‐mediated degranulation of mouse bone marrow‐derived mast cells (BMMCs) and anaphylaxis (Bansal et al Nat Immunol in press). To determine how RGS13 affected GPCR‐mediated signal transduction in human mast cells, we examine responses of the human mastocytoma cell line (HMC‐1) overexpressing RGS13 or expressing an RGS13‐specific short, hairpin siRNA (shRNA) to GPCR stimulation. Compared to control cells, HMC‐1 cells with reduced RGS13 amounts exhibited heightened Ca2+ influx in response to adenosine, C5a, sphingosine‐1‐phosphate (S‐1P), and CXCL12. Chemotaxis and cytokine (interleukin 8, IL‐8) secretion were increased in shRGS13‐HMC‐1 cells while overexpression of RGS13 in HMC‐1 cells inhibited CXCL12‐induced Ca2+ mobilization and chemotaxis. These results suggest that RGS13 may exert control over GPCR‐evoked biological responses in human mast cells.