title: Novel biphasic role of LipoxinA(4) on 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 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.
authors.affiliation: Department of Anaesthesia, Second Affiliated Hospital of WenZhou Medical College, Zhejiang 325003, China.
authors.forename: Shengxing
authors.initials: S
authors.lastname: Zheng
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Qian
authors.initials: Q
authors.lastname: He
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Song
authors.forename: Duyun
authors.initials: D
authors.lastname: Ye
authors.forename: Fang
authors.initials: F
authors.lastname: Gao
authors.forename: Shengwei
authors.initials: S
authors.lastname: Jin
authors.forename: Qingquan
authors.initials: Q
authors.lastname: Lian
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000276:immunology / Q000494:pharmacology; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000276:immunology*; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D044045:Lipoxins / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D008168:Lung / Q000166:cytology*; D015230:Prostaglandin D2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044067:Receptors, Lipoxin / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D044045:Lipoxins; D044067:Receptors, Lipoxin; C482540:lipoxin A(4) receptor, rat; C040527:lipoxin A4; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D015232:Dinoprostone; D015230:Prostaglandin D2