An essential role of syntaxin 3 protein for granule exocytosis and secretion of IL‐1α, IL‐1β, IL‐12b, and CCL4 from differentiated HL‐60 cells

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

关键词: SNARE proteins;    neutrophils;    gelatinase granules;    cytokines;    extracellular release;   

DOI  :  10.1189/jlb.3A0514-254RR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Besidestheirrolesinthekillingofpathogens,neutrophilshavethecapacitytopackageavarietyofcytokinesintocytoplasmicgranulesforsubsequentreleaseuponinflammatoryconditions.Becausetherapidsecretionofcytokinesorchestratestheactionofotherimmunecellsattheinfectionsiteandthus,cancontributetothedevelopmentandchronicityofinflammatorydiseases,weaimedtodeterminetheintracellularSNAREmachineryresponsiblefortheregulationofcytokinesecretionanddegranulation.Fromaconstructedgene‐expressionnetwork,wefirstselectedrelevantcytokinesforfunctionalvalidationbytheCBAapproach.Weestablishedacytokine‐secretionprofileforhumanneutrophilsanddHL‐60cells,underliningtheirsimilarabilitytosecreteabroadvarietyofcytokineswithinproinflammatoryconditionsmimickedbyLPSstimulation.Secondly,afterscreeningofSNAREgenesbymicroarrayexperiments,weselectedSTX3forfurtherfunctionalstudies.WiththeuseofasiRNAstrategy,weshowthatSTX3isclearlyrequiredforthemaximalreleaseofIL‐1α,IL‐1β,IL‐12b,andCCL4withoutalterationofothercytokinesecretionindHL‐60cells.Inaddition,wedemonstratethatSTX3isinvolvedinMMP‐9exocytosisfromgelatinasegranules,whereSTX3ispartlylocalized.OurresultssuggestthatthesecretionofIL‐1α,IL‐1β,IL‐12b,andCCL4occursduringgelatinasedegranulation,aprocesscontrolledbySTX3.Insummary,thesefindingsprovidefirstevidencethatSTX3hasanessentialroleintraffickingpathwaysofcytokinesinneutrophilgranulocytes...

【 授权许可】

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