Sequential induction of pro- and anti-inflammatory prostaglandins and peroxisome proliferators-activated receptor-gamma during normal wound healing: A time course study

Lipid mediators generated from metabolism of arachidonic acid play a crucial role in the initiating and resolution of acute inflammation by shifting from pro-inflammatory prostaglandin (PG) E-2 to anti-inflammatory PGD(2) and its metabolites. The changes in PG levels over time during the normal wound-repair process have not, however, been reported. We determined the temporal expression of PG and their biosynthetic enzymes using the full thickness incisional model of normal wound healing in mice. We demonstrate that during normal wound repair, there is a shift in the metabolism of arachidonate from PGE(2) during the acute inflammatory phase to PGD(2) during the repair phase. This shift is mediated by temporal changes in the expression of cyclooxygenases (COX) and microsomal PGES (mPGES)-1. Inducible COX (COX-2) expression is sustained throughout the initiation and repair process, but mPGES-1 is increased only during the acute inflammatory phase and its disappearance coincides with increased PGD(2). PGD(2) and its degradation products are known to mediate their anti-inflammatory effects by binding to peroxisome proliferators-activated receptor gamma (PPAR gamma). In this study, we show that PPAR gamma is upregulated during the resolution phase of wound repair concomitant with the shift to PGD(2), and may be responsible for initiating endogenous mechanism resulting in healing/resolution. (c) 2006 Elsevier Ltd. All rights reserved.