Novel biphasic role of LipoxinA(4) on expression of cyclooxygenase-2 in lipopolysaccharide-stimulated lung fibroblasts

Research output: Contribution to journalArticle

Authors

  • Shengxing Zheng
  • Qian Wang
  • Qian He
  • Xiaorong Song
  • Duyun Ye
  • Shengwei Jin
  • Qingquan Lian

Colleges, School and Institutes

Abstract

Fibroblasts are important to host defence and immunity, can also as initiators of inflammation as well. As the endogenous "braking signal", Lipoxins can regulate anti-inflammation and the resolution of inflammation. We investigated the effect of lipoxinA(4) on the expression of cyclooxygenase-2 in lipopolysaccharide-stimulated lung fibroblasts. We demonstrated that the expression of cyclooxygenase-2 protein was significantly increased and peaked initially at 6 hours, with a second increase, with maximal levels occurring 24 hours after lipopolysaccharide challenge. ProstaglandinE(2) levels also peaked at 6 hours, and prostaglandinD(2) levels were increased at both 6 and 24 hours. Exogenous lipoxinA(4) inhibited the first peak of cyclooxygenase-2 expression as well as the production of prostaglandinE(2) induced by lipopolysaccharide in a dose-dependent manner. In contrast, exogenous lipoxinA(4) increased the second peak of cyclooxygenase-2 expression as well as the production of prostaglandinD(2) induced by lipopolysaccharide in a dose-dependent manner. LipoxinA(4) receptor mRNA expression was markedly stimulated by lipopolysaccharide but inhibited by lipoxinA(4). We present evidence for a novel biphasic role of lipoxinA(4) on the expression of cyclooxygenase-2 in lipopolysaccharide-stimulated lung fibroblasts, whereby LXA(4) has an anti-inflammatory and proresolving activity in lung fibroblasts following LPS stimulation.

Details

Original languageEnglish
Pages (from-to)745340
JournalMediators of Inflammation
Volume2011
Publication statusPublished - 2011

Keywords

  • Animals, Anti-Inflammatory Agents, Cells, Cultured, Cyclooxygenase 2, Dinoprostone, Dose-Response Relationship, Drug, Fibroblasts, Gene Expression Regulation, Enzymologic, Lipopolysaccharides, Lipoxins, Lung, Prostaglandin D2, Rats, Rats, Sprague-Dawley, Receptors, Lipoxin, Up-Regulation