Kapoor Mohit, Kojima Fumiaki, Yang Lihua, Crofford Leslie J
Department of Internal Medicine, Division of Rheumatology, Room J-509, Kentucky Clinic, University of Kentucky, Lexington, KY 40536-0284, USA.
Prostaglandins Leukot Essent Fatty Acids. 2007 Feb;76(2):103-12. doi: 10.1016/j.plefa.2006.11.006. Epub 2007 Jan 18.
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) E2 to anti-inflammatory PGD2 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 PGE2 during the acute inflammatory phase to PGD2 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 PGD2. PGD2 and its degradation products are known to mediate their anti-inflammatory effects by binding to peroxisome proliferators-activated receptor gamma (PPARgamma). In this study, we show that PPARgamma is upregulated during the resolution phase of wound repair concomitant with the shift to PGD2, and may be responsible for initiating endogenous mechanism resulting in healing/resolution.
由花生四烯酸代谢产生的脂质介质，通过从促炎性前列腺素（PG）E2转变为抗炎性PGD2及其代谢产物，在急性炎症的起始和消退过程中发挥关键作用。然而，正常伤口修复过程中PG水平随时间的变化尚未见报道。我们使用小鼠正常伤口愈合的全层切口模型，确定了PG及其生物合成酶的时间表达。我们证明，在正常伤口修复过程中，花生四烯酸的代谢从急性炎症期的PGE2转变为修复期的PGD2。这种转变由环氧化酶（COX）和微粒体PGES（mPGES）-1表达的时间变化介导。诱导型COX（COX-2）的表达在整个起始和修复过程中持续存在，但mPGES-1仅在急性炎症期增加，其消失与PGD2的增加同时发生。已知PGD2及其降解产物通过与过氧化物酶体增殖物激活受体γ（PPARγ）结合来介导其抗炎作用。在本研究中，我们表明PPARγ在伤口修复的消退期上调，与向PGD2的转变同时发生，并且可能负责启动导致愈合/消退的内源性机制。
