Up-regulation of heme oxygenase-1 expression through the Rac1/NADPH oxidase/ROS/p38 signaling cascade mediates the anti-inflammatory effect of 15-deoxy-Δ12,14-prostaglandin J2 in murine macrophages

We investigated the signaling pathway that leads to the expression of heme oxygenase-1 (HO-1) in murine macrophages in response to 15-deoxy-Delta(12,14)-prostagiandin J(2) (15dPGJ(2)). 15dPGJ(2) caused dose- and time-dependent activation of Rac1, followed by a transient increase in reactive oxygen species (ROS) via NADPH oxidase, which leads to downstream activation of p38 kinase. Inhibition of 15dPGJ(2)-dependent HO-1 expression significantly attenuated suppression by 15dPGJ(2) Of LPS-induced iNOS expression and subsequent production of nitric oxide (NO). Our findings strongly suggest that 15dPGJ(2) exerts its anti-inflammatory activity through the Rac1-NADPH oxidase-ROS-p38 signaling to the up-regulation of HO-1 in an in vitro inflammation model. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.