IL-33 and MRGPRX2-Triggered Activation of Human Skin Mast Cells-Elimination of Receptor Expression on Chronic Exposure, but Reinforced Degranulation on Acute Priming.

ABSTRACT: Clinically relevant exocytosis of mast cell (MC) mediators can be triggered by high-affinity IgE receptor (FcεRI)-aggregation (allergic route) or by the so-called pseudo-allergic pathway elicited via MAS-related G protein-coupled receptor-X2 (MRGPRX2). The latter is activated by drugs and endogenous neuropeptides. We recently reported that FcεRI-triggered degranulation is attenuated when human skin mast cells are chronically exposed to IL-33. Here, we were interested in the regulation of the MRGPRX2-route. Chronic exposure of skin MCs to IL-33 basically eliminated the pseudo-allergic/neurogenic route as a result of massive MRGPRX2 reduction. This downregulation seemed to partially require c-Jun N-terminal Kinase (JNK), but not p38, the two kinases activated by IL-33 in skin MCs. Surprising

SUBMITTER: Wang Z 

PROVIDER: S-EPMC6523246 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature