Coordinated induction of cyclooxygenase‐2/prostaglandin E2 and hepatocyte growth factor by apoptotic cells prevents lung fibrosis

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: TGF‐;    β;    alveolar macrophages;    pulmonary fibrosis;    bleomycin;    mice;   

DOI  :  10.1189/jlb.0513255

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

ApoptoticcellinstillationafterbleomycininducespersistentHGFproductionandprotectsfrompulmonaryfibrosis,buttheunderlyingmechanismremainsunclear.Weinvestigatedimmediateandprolongedeffectsofinvivoinstillationofapoptoticcellsintobleomycin‐stimulatedmouselungs(2daysold)onCOX‐2expressioninlungtissueandalveolarmacrophagesandPGE2productioninBALF.Furthermore,functionalinteractionbetweenthesemoleculesandHGF,followingapoptoticcellinstillationinableomycin‐inducedlungfibrosismodel,wasassessed.ApoptoticcellinstillationresultsinenhancedimmediateandprolongedexpressionofCOX‐2andPGE2whencomparedwiththosefrombleomycin‐only‐treatedmice.CoadministrationoftheCOX‐2‐selectiveinhibitorNS398ortheselectivePGE2REP2inhibitorAH6809inhibitedtheincreaseinHGFproduction.InhibitionofHGFsignalingusingPHA‐665752inhibitedincreasesinCOX‐2andPGE2.Long‐terminhibitionofCOX‐2,PGE2,orHGFreversedthereductionofTGF‐β,apoptoticandMPOactivities,proteinlevels,andhydroxyprolinecontents.Up‐regulationofCOX‐2/PGE2andHGFthroughapositive‐feedbackloopmaybeanimportantmechanismwherebyapoptoticcellinstillationexertsthenetresultsofanti‐inflammatory,antiapoptotic,andantifibroticaction...

【 授权许可】

CC BY