Proteasome Inhibition Augments Cigarette Smoke-Induced GM-CSF Expression in Trophoblast Cells via the Epidermal Growth Factor Receptor 英文参考文献.docVIP
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ProteasomeInhibitionAugmentsCigaretteSmoke-
InducedGM-CSFExpressioninTrophoblastCellsviathe
EpidermalGrowthFactorReceptor
Ya-YuanFu1,JenniferC.Nergard2,NicoleK.Barnette2,Yan-LingWang1,KarlX.Chai2,Li-MeiChen2*
1StateKeyLaboratoryofReproductiveBiology,InstituteofZoology,ChineseAcademyofSciences,Beijing,People’sRepublicofChina,2BurnettSchoolofBiomedical
Sciences,UniversityofCentralFloridaCollegeofMedicine,Orlando,Florida,UnitedStatesofAmerica
Abstract
Maternalcigarettesmokinghasadverseeffectsonpregnancyoutcomes.Thegranulocyte-macrophagecolony-stimulating
factor(GM-CSF)isanessentialcytokineforanormalpregnancy.Weinvestigatedtheimpactofcigarettesmokeextract(CSE)
on GM-CSF expression in human cytotrophoblast cells and suggested a cellular mechanism underlying the CSE-induced
GM-CSFexpression.Animmortalizednormalhumantrophoblastcellline(B6Tert-1)wastreatedwithCSE.Theviabilityand
proliferationoftheCSE-treatedB6Tert-1cellswereevaluated,andtheexpressionofGM-CSFinthesecellswasquantifiedat
themRNAandtheproteinlevelsbymeansofreverse-transcriptionandquantitativepolymerasechainreaction(RT-qPCR);
andenzyme-linkedimmunosorbentassay(ELISA),respectively.HumantrophoblastcellstreatedwithCSEhadanincreased
expressionofGM-CSFatboththemRNAandtheproteinlevels.TheCSE-inducedGM-CSFexpressionwassynergistically
enhanced by the addition of the proteasome inhibitor MG-132, but inhibited by AG-1478, an inhibitor of the epidermal
growthfactorreceptor(EGFR)kinase.Furthermore,CSEtreatmentincreasedthephosphorylationoftheextracellular-signal
regulated kinases (ERK1/2) in the trophoblast cells. The expression of other growth factors such as heparin-binding
epidermalgrowthfactor-likegrowthfactor(HB-EGF)andvascularendothelialgrowthfactor(VEGF)wasalsoevaluated.Our
datasuggestedthatcigarettesmokingandproteasomeinhibitionsynergisticallyup-regulateGM-CSFcytokineexpression
byactivatingtheEGFRsignalingpathway.
Citation: Fu Y-Y,Nergard JC,BarnetteNK,Wang Y-L,ChaiKX,et al.(2012)ProteasomeInhibitionAugmentsCigar
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