Novel roles of lipid mediators in psoriatic skin inflammation

Abstract

Abstract Psoriasis is a common chronic inflammatory cutaneous disease thought to arise as a result of infiltration of inflammatory cells and activation of keratinocytes. Psoriasis has been considered as a classical Th1 disease; however, Th17 cells are attracting much interest. Previous knowledge on the pathology of psoriasis has been obtained mostly through the study of human data and samples. In addition, recently developed animal models for psoriatic skin inflammation recapitulates the hallmarks of human psoriasis and provide us new insights on psoriasis. Lipid mediators and their receptors regulate a variety of physiological processes and involved in multiple pathologies including immune-related diseases. Here, we explored novel lipid mediators involved in psoriatic skin inflammation using clinical samples and imiquimod-induced psoriasis model. In particular, mass spectrometry analysis for multiplex quantitation of eicosanoids using imiquimod-treated murine skin samples revealed unique kinetics of various lipid mediators in the time-series from early induction phase to chronic resolution phase. These data motivated us to focus on some lipid mediators such as leukotriene B4 (LTB4) and prostaglandin E2 (PGE2). As an example, BLT1 (known as LTB4 receptor) and CXCR2 have been revealed to coordinately promote neutrophil infiltration into the skin during the early phase of imiquimod-induced inflammation. Further analysis on PGE2 is in progress and some data indicates the novel functions of PGE2 and mPGES-1, an upstream enzyme for PGE2 production, in the pathogenesis in psoriasis. These insights may aid in the rational design of novel treatments for broad spectrum of inflammatory and immune disorders beyond psoriasis.