Rhinovirus-induced basic fibroblast growth factor release mediates airway remodeling features 英文参考文献.docVIP

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Rhinovirus-induced basic fibroblast growth factor release mediates airway remodeling features 英文参考文献.doc

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Rhinovirus-induced basic fibroblast growth factor release mediates airway remodeling features 英文参考文献

Skevakietal.ClinicalandTranslationalAllergy2012,2:14 /content/2/1/14 RESEARCH OpenAccess Rhinovirus-inducedbasicfibroblastgrowthfactor releasemediatesairwayremodelingfeatures ChrysanthiLSkevaki1*,SteliosPsarras2,EleniVolonaki1,HarrisPratsinis3,IriniSSpyridaki1,MinaGaga4, VassilikiGeorgiou1,StylianosVittorakis4,AuricaGTelcian5,ParaskeviMaggina1,DimitrisKletsas3, DimitriosGourgiotis1,SebastianLJohnston5andNikolaosGPapadopoulos1 Abstract Background:Humanrhinoviruses,majorprecipitantsofasthmaexacerbations,inducelowerairwayinflammation andmediateangiogenesis.Thepurposeofthisstudywastoassessthepossibilitythatrhinovirusesmayalso contributetothefibroticcomponentofairwayremodeling. Methods:Levelsofbasicfibroblastgrowthfactor(bFGF)mRNAandproteinweremeasuredfollowingrhinovirus infectionofbronchialepithelialcells.TheprofibroticeffectofepithelialproductswasassessedbyDNAsynthesis andmatrixmetalloproteinaseactivityassays.Moreover,epithelialcellswereexposedtosupernatantsfromcultured peripheralbloodmononuclearcells,obtainedfromhealthydonorsoratopicasthmaticsubjectsandsubsequently infectedbyrhinovirusandbFGFreleasewasestimated.bFGFwasalsomeasuredinrespiratorysecretionsfrom atopicasthmaticpatientsbeforeandduringrhinovirus-inducedasthmaexacerbations. Results:RhinovirusepithelialinfectionstimulatedmRNAexpressionandreleaseofbFGF,thelatterbeingpositively correlatedwithcelldeathunderconditionspromotingrhinovirus-inducedcytotoxicity.Supernatantsfrominfected culturesinducedlungfibroblastproliferation,whichwasinhibitedbyanti-bFGFantibody,anddemonstrated increasedmatrixmetalloproteinaseactivity.Rhinovirus-mediatedbFGFreleasewassignificantlyhigherinaninvitro simulationofatopicasthmaticenvironmentand,importantly,duringrhinovirus-associatedasthmaexacerbations. Conclusions:RhinovirusinfectioninducesbFGFreleasebyairwayepithelium,andstimulatesstromacell proliferationcontributingtoairwayremodelinginasthma.Repeatedrhinovirusinfectionsmaypromoteasthma persistence,particularlyinthecontextofatopy;preve