Interleukin‐17A differentially modulates BCG induction of cytokine production in human blood macrophages

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: helper T cells;    tuberculosis;    inflammation;   

DOI  :  10.1189/jlb.0510311

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

ThepathogenesisofMtbdependsinpartoncytokinecross‐regulationbetweenmacrophagesandTcellsinhostimmunity.Th17cellsproduceIL‐17Atoinducegranulomaformationandtorestrictmycobacterialdissemination.IL‐17AalsomediatescytokineresponsesinducedbyproinflammatorycytokinessuchasTNF‐α.OurpreviousresultsshowedthatBCGinducesIL‐6,IL‐10,andTNF‐αviaactivityofproteinkinases,includingdsRNA‐activatedserine/threonineproteinkinaseandglycogensynthasekinase‐3inprimaryhumanmonocytes.Therefore,weinvestigatedwhetherIL‐17A,uponitsinductionbyBCG,playsanadditionalroletoaidtheproductionofdownstreamproinflammatorycytokinesinmacrophages.Here,weshowedthatIL‐17AenhancedIL‐6mRNAandproteinlevelsinduciblebyBCGinatime‐anddose‐dependentmanner,whereasithadnoeffectonIL‐10andTNF‐αproduction.WealsodemonstratedthatIL‐17AactivatedthephosphorylationofERK1/2triggeredbyBCG.WiththeuseofaspecificchemicalinhibitorofaMAPK/ERK‐activatingkinase(MEK1/2),weconfirmedthecorrelationbetweentheenhancedERK1/2activationandaugmentedIL‐6production.Additionally,werevealedthatIL‐17AactsinconcertwithBCG‐inducedTNF‐αtoenhancethelevelofIL‐6synthesis.Takentogether,ourresultssuggestasignificantroleofIL‐17Atoserveasamodulatorofcytokineexpressionininnateimmuneresponseduringmycobacterialinfection...

【 授权许可】

CC BY