Role of Sphingosine-1-Phosphate in Mast Cell Functions and Asthma and Its Regulation by Non-Coding RNA

Sphingolipid metabolites are emerging as important signaling molecules in allergic diseases specifically asthma. One of the sphingolipid metabolite, sphingosine-1-phosphate (S1P) is involved in cell differentiation, proliferation, survival, migration and angiogenesis. In the allergic diseases, alteration of S1P levels influence the differentiation and responsiveness of mast cells (MCs). S1P is synthesized by two sphingosine kinases (SphKs), SphK1 and SphK2. Engagement of IgE to the FceRI receptor induces the activation of both the SphKs and generates sphingosine-1-phosphate (S1P). Furthermore, SphKs are also essential to FceRI-mediated MC activation. Activated MCs export S1P into the extracellular space, and causes inflammatory response and tissue remodeling. S1P signaling has dual role in allergic responses. Activation of SphKs and secretion of S1P is required for MC activation; however, S1P signaling plays a vital role in the recovery from anaphylaxis. Several non-coding RNAs have been shown to play a crucial role in controlling the MCs associated inflammatory and allergic responses. Thus, S1P signaling pathway and its regulation by non-coding RNA could be explored as an exciting potential therapeutic target for asthma and other MCs-associated diseases.