Proinflammatory stimulants promote the expression of a promiscuous G protein-coupled receptor, mFPR2, in microvascular endothelial cells.

Human formylpeptide receptor 2 (FPR2) and its mouse homologue mFPR2 belong to the G protein-coupled, seven-transmembrane receptor superfamily. Both FPR2 and mFPR2 recognize a variety of exogenous and host-derived chemotactic peptides associated with proinflammatory conditions. Since endothelial cells actively participate in inflammation, we investigated whether microvascular endothelial cells express mFPR2 and its regulation by proinflammatory factors. We found that resting primary mouse microvascular endothelial cells and a cell line bEnd.3 expressed low levels of mFPR2 at both mRNA and protein levels, which was markedly enhanced by two key proinflammatory stimulants, lipopolysaccharide (LPS) and interleukin (IL)-1β. While the inductive effect of LPS was dependent on the JNK MAP kinase, both JNK and ERK MAP kinases were utilized by IL-1β to enhance mFPR2 expression. Overexpression of dominant-negative IκBα attenuated LPS- and IL-1β-induced mFPR2 expression, indicating an essential role for NF-κB in regulating mFPR2 expression in endothelial cells by proinflammatory stimulants. Our results suggest that upregulated mFPR2 in vascular endothelial cells under inflammatory conditions may mediate cell responses in diseases in which mFPR2 agonists are elevated.