Resolution of PMA-Induced Skin Inflammation Involves Interaction of IFN-γand ALOX15

Abstract

Background.Acute inflammation and its timely resolution play important roles in the body’s responses to the environmental stimulation. Although IFN-γis well known for the induction of inflammation, its role in the inflammation resolution is still poorly understood.Methodology and Principal Findings.In this study, we investigated the function of interferon gamma (IFN-γ) during the resolution of PMA-induced skin inflammationin vivo. The results revealed that the expression levels of IL-6, TNF-α, and monocyte chemoattractant protein 1 (MCP-1) in skin decreased during the resolution stage of PMA-induced inflammation, while IFN-γis still maintained at a relatively high level. Neutralization of endogenous IFN-γled to accelerated reduction of epidermal thickness and decreased epithelial cell proliferation. Similarly, decreased infiltration of inflammatory cells (Gr1+or CD11b+cells) and a significant reduction of proinflammatory cytokines were also observed upon the blockade of IFN-γ. Furthermore, neutralization of IFN-γboosted ALOX15 expression of the skin during inflammation resolution. In accordance, application of lipoxin A4 (LXA4, a product of ALOX15) obtained a proresolution effect similar to neutralization of IFN-γ. These results demonstrated that through upregulating ALOX15-LXA4 pathway, blockage of IFN-γcan promote the resolution of PMA-induced skin inflammation.