Novel Biphasic Role of LipoxinA4on Expression of Cyclooxygenase-2 in Lipopolysaccharide-Stimulated Lung Fibroblasts

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 lipoxinA4on 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. ProstaglandinE2levels also peaked at 6 hours, and prostaglandinD2levels were increased at both 6 and 24 hours. Exogenous lipoxinA4inhibited the first peak of cyclooxygenase-2 expression as well as the production of prostaglandinE2induced by lipopolysaccharide in a dose-dependent manner. In contrast, exogenous lipoxinA4increased the second peak of cyclooxygenase-2 expression as well as the production of prostaglandinD2induced by lipopolysaccharide in a dose-dependent manner. LipoxinA4receptor mRNA expression was markedly stimulated by lipopolysaccharide but inhibited by lipoxinA4. We present evidence for a novel biphasic role of lipoxinA4on the expression of cyclooxygenase-2 in lipopolysaccharide-stimulated lung fibroblasts, whereby LXA4has an anti-inflammatory and proresolving activity in lung fibroblasts following LPS stimulation.