MiR-155 has positive and negative roles on cytokine production in mast cells

Abstract

Abstract Mast cells play a critical role in allergic inflammation by releasing preformed mediators such as histamine and serine neutral proteases, biosynthesizing lipid mediators like prostaglandins and leukotrienes, and synthesizing new cytokines. MicroRNA-155 (miR-155) plays a key regulatory role in the pathogenesis of allergy. The aim of this study was to investigate the biological functions of miR-155 on mast cell mediator release. MiR-155 was increased in human skin mast cells following FcɛRI crosslinking. To explore the role of miR-155 on mast cells function, we used bone marrow-derived mast cells (BMMCs) from wild type, miR-155 KO, and miR-155 Tg mice. MiR-155 had no effect on FcɛRI-induced mast cell degranulation. On the other hand, FcɛRI-induced COX-2 was significantly diminished in the absence of miR-155 suggesting that miR-155 plays a critical role in Prostaglandin D2 biosynthesis. FcɛRI-induced cytokine production was diminished in miR-155 KO BMMCs compared to WT. Interestingly, cytokine production from miR-155 KO BMMCs was increased compared to WT following LPS treatment. These findings indicate that miR-155 acts as a positive regulator in the FcɛRI pathway, and a negative regulator of the TLR4 pathway in mast cells. Current studies are aimed at determining how miR-155 functions in these pathways.