国外最新医学摘要.pdf

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1、世界最新医学信息文摘2014年第14卷第7期国外最新医学摘要●Phosphodiesterase-4inhibitionimprovescorticosteroidinsensitivityinpulmonaryendothelialceHsunderoxidativestressJ．L．Ortiz，J．Milara，J．Lluch，A．DeDiego，C．SanzandJ．Con~oABSTRACTBackgroundSeveralclinicalstudieshaveshownthatsmokinginasthmaticsandchronicobstructivepulmonar

2、ydiseasepatientsiscloselyassociatedwithcorticosteroidrefractoriness．Inthiswork．wehaveanalyzedglucocorticoidinsensitivityinhumanpulmonaryarteryendothelialcells(HPAECs)undercigarettesmokeextract(CSE)exposureaswellasthepossibleadditiveefectsofthecombinationtherapywithaphosphodiesterase(PDE)．4inhib

3、itor．MethodsInterleukin(IL)一8wasmeasuredincellsupernatantsbyELISA．Histonedeacetylase(HDAC)，histoneacetylase(HAT)，andin仃acellularcAMPlevelsweremeasuredbycolorimetricassaysandenzymeimmunoassay,respectively．PDE4isotypesandglucocorticoidreceptor(G]．0【and13expressionweremeasuredbyrea1．timeR_T．PCR．Re

4、sultsThePDE4inhibitorrolipramdosedependentlyinhibitedtheIL．8secretioninducedbyCSE5％．Incontrast．dexamethasone1u1didnotshowinhibitoryefectonIL。8secretion．Combinationofsubeffectiverolipramconcentrationsatl0nMincreasedtheinhibitoryefectofdexamethasoneto—45％ofinhibition．Cigaretesmokeextract5％inhibit

5、edHDACactivityandincreasedHATactivitygeneratingglucocorticoidinsensitivity．RolipramdidnotmodifytheHDACactivity,howeverpartiallyinhibitedtheincreaseinHATactivityat1rdV1．PDE4isotypeswereup—regulatedbyCSE5％withtheconsequentcA．MPdown-regulation．Dexamethasonereducedal1PDE4isotypesexpressionandshowed

6、additiveeffectswithrolipramenhancingcAMPlevels．Furthermore，rolipramenhancedGR．aexpressionandinhibitedtheincreaseinGR．BinducedbyCSE．ConclusionsCombinationofrolipramanddexamethasoneshowsadditivepropertiesinHPAECsunderglucocorticoidinsensitiveconditions．TheseresultsmaybeOfpotentialvalueinfutureant

7、i．inflammatOrytherapiesusingcombinationofPDE4inhibitorsandglucocorticoids．LipidsarerequiredforthedevelopmentofBrazilnutallergy：theroleofmouseandhumaniNKTcellsL．Mirotti，E．Florsheim，L．Rundqvist，G．Larsson，F．Spinozzi，M．Leite-de-Moraes