Respiratory Syncytial Virus Inhibits Ciliagenesis in Differentiated Normal Human Bronchial Epithelial Cells Effectiveness of N-Acetylcysteine 英文参考文献.docVIP

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Respiratory Syncytial Virus Inhibits Ciliagenesis in Differentiated Normal Human Bronchial Epithelial Cells Effectiveness of N-Acetylcysteine 英文参考文献.doc

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Respiratory Syncytial Virus Inhibits Ciliagenesis in Differentiated Normal Human Bronchial Epithelial Cells Effectiveness of N-Acetylcysteine 英文参考文献

RespiratorySyncytialVirusInhibitsCiliagenesisin DifferentiatedNormalHumanBronchialEpithelialCells: EffectivenessofN-Acetylcysteine ManuelMata1,2*,IreneSarrion1,MiguelArmengot3,4,CarmenCarda3,IsidoroMartinez2,5, JoseA.Melero2,6,JulioCortijo1,2,3 1ResearchFoundationoftheUniversityGeneralHospitalofValencia,Valencia,Spain,2CentrodeInvestigacio′nBiome′dicaenRed(CIBER)deEnfermedadesRespiratorias, Valencia,Spain,3UniversityofValencia,Valencia,Spain,4UniversityGeneralHospitalofValencia,Valencia,Spain,5UnidaddeInteraccio′nVirus-Ce′lula,CentroNacional deMicrobiolog?′a,InstitutodeSaludCarlosII,Madrid,Spain,6UnidaddeBiolog?′aViral,CentroNacionaldeMicrobiolog?′a,InstitutodeSaludCarlosII,Madrid,Spain Abstract Persistentrespiratorysyncytialvirus(RSV)infectionshavebeenassociatedwiththeexacerbationofchronicinflammatory diseases,includingchronicobstructivepulmonarydisease(COPD).Thisvirusinfectstherespiratoryepithelium,leadingto chronicinflammation, andinducesthereleaseofmucins andtheloss ofciliaactivity,twofactorsthatdeterminemucus clearanceandtheincreaseinsputumvolume.Thesealterationsinvolvereactiveoxygenspecies-dependentmechanisms. TheantioxidantN-acetylcysteine(NAC)hasprovenusefulinthemanagementofCOPD,reducingsymptoms,exacerbations, and accelerated lung function decline. NAC inhibits RSV infection and mucin release in human A549 cells. The main objectiveofthisstudywastoanalyzetheeffectsofNACinmodulatingciliaryactivity,ciliagenesis,andmetaplasiainprimary normal human bronchial epithelial cell (NHBEC) cultures infected with RSV. Our results indicated that RSV induced ultrastructural abnormalities in axonemal basal bodies and decreased the expression of b-tubulin as well as two genes involvedinciliagenesis,FOXJ1andDNAI2.Thesealterationsledtoadecreaseinciliaryactivity.Furthermore,RSVinduced metaplasticchangestotheepitheliumandincreasedthenumberofgobletcellsandtheexpressionofMUC5ACandGOB5. NAC restored the normal functions of the epithelium, inhibiting ICAM1 expression, subsequent R