Novel biphasic role of LipoxinA(4) on expression of cyclooxygenase-2 in lipopolysaccharide-stimulated lung fibroblasts
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Colleges, School and Institutes
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.
|Journal||Mediators of Inflammation|
|Publication status||Published - 2011|
- 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