15(S)-HETE plays a regulatory role in the immune inflammatory responses

Abstract

Abstract Arachidonic acids are subjected to the enzymatic transformation by PGH2 synthase or lipoxygenase upon the liberation from the membrane phospholipid. Using in vitro and in vivo experimental models, we have investigated the cellular and molecular mechanisms in the production and function of arachidonic acid metabolites. Here we report that a downstream product of 15-lipoxygenase, 15-S-hydroxyeicosatetraenoic acid (15-S-HETE) is not produced by human follicular dendritic cell (FDC)-like cells but exerts a regulatory effect on prostaglandin production by this type of cells. 15-S-HETE appears to derive from endothelial cells. FDC-like cells, which were isolated from human tonsil, do not express 15-lipoxyenase or 5-lipoxygenase but metabolize 15-S-HETE into downstream products. Immunoblotting analysis and results with chemical inhibitors imply that 15-S-HETE acts on FDC-like cells via PPAR-γ and leukotriene B4 receptor 2. 15-S-HETE enhances or inhibits the expression of PGH2 synthase and resultant prostaglandin production in FDC-like cells, which depends on the types of co-stimulation. Based on these data, we suggest a novel cellular and molecular pathway of immune regulation mediated by arachidonic acid metabolites.