MMP28 promotes macrophage polarization toward M2 cells and augments pulmonary fibrosis

[摘要] MembersoftheMMPfamilyfunctioninvariousprocessesofinnateimmunity,particularlyincontrollingimportantstepsinleukocytetraffickingandactivation.MMP28(epilysin)isamemberofthisfamilyofproteinases,andwehavefoundthatMMP28isexpressedbymacrophagesandregulatestheirrecruitmenttothelung.WehypothesizedthatMMP28regulatesotherkeymacrophageresponses,suchasmacrophagepolarization.Furthermore,wehypothesizedthattheseMMP28‐dependentchangesinmacrophagepolarizationwouldalterfibroticresponsesinthelung.WeexaminedthegeneexpressionchangesinWTandMmp28−/−BMDMs,stimulatedwithLPSorIL‐4/IL‐13topromoteM1andM2cells,respectively.WealsocollectedmacrophagesfromthelungsofPseudomonasaeruginosa‐exposedWTandMmp28−/−micetoevaluatechangesinmacrophagepolarization.Lastly,weevaluatedthemacrophagepolarizationphenotypesduringbleomycin‐inducedpulmonaryfibrosisinWTandMmp28−/−miceandassessedmicefordifferencesinweightlossandtotalcollagenlevels.WefoundthatMMP28dampensproinflammatorymacrophagefunctionandpromotsM2programming.Inbothinvivomodels,wefounddeficitsinM2polarizationinMmp28−/−mice.Inbleomycin‐inducedlunginjury,thesechangeswereassociatedwithreducedfibrosis.MMP28isanimportantregulatorofmacrophagepolarization,promotingM2function.LossofMMP28resultsinreducedM2polarizationandprotectionfrombleomycin‐inducedfibrosis.ThesefindingshighlightanovelroleforMMP28inmacrophagebiologyandpulmonarydisease...

[学科分类] 生理学

[关键词] M1;inflammation;monocytes;epilysin