CD26/dipeptidylpeptidase IV—chemokine interactions: double‐edged regulation of inflammation and tumor biology

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

关键词: post‐;    translational modification;    leukocyte;    protease;    chemotaxis;   

DOI  :  10.1189/jlb.3MR0915-401R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Post‐translationalmodificationofchemokinesisanessentialregulatorymechanismtoenhanceordampentheinflammatoryresponse.CD26/dipeptidylpeptidaseIV,ubiquitouslyexpressedintissuesandblood,removesNH2‐terminaldipeptidesfromproteinswithapenultimateProorAla.Alargenumberofhumanchemokines,includingCXCL2,CXCL6,CXCL9,CXCL10,CXCL11,CXCL12,CCL3L1,CCL4,CCL5,CCL11,CCL14,andCCL22,arecleavedbyCD26;however,theefficiencyisclearlyinfluencedbytheaminoacidssurroundingthecleavagesiteandalthoughnotyetproven,potentiallyaffectedbythechemokineconcentrationandinteractionswiththirdmolecules.NH2‐terminalcleavageofchemokinesbyCD26hasprominenteffectsontheirreceptorbinding,signaling,andhence,invitroandinvivobiologicactivities.However,ratherthanhavingasimilarresult,theoutcomeofNH2‐terminaltruncationishighlydiverse.Eithernodifferenceinactivityordrasticalterationsinreceptorrecognition/specificityandhence,chemotacticactivityareobserved.Analogously,chemokine‐dependentinhibitionofHIVinfectionisenhanced(forCCL3L1andCCL5)ordecreased(forCXCL12)byCD26cleavage.TheoccurrenceofCD26‐processedchemokineisoformsinplasmaunderscorestheimportanceoftheinvitro‐observedCD26cleavages.Throughmodulationofchemokineactivity,CD26regulatesleukocyte/tumorcellmigrationandprogenitorcellreleasefromthebonemarrow,asshownbyuseofmicetreatedwithCD26inhibitorsorCD26knockoutmice.AschemokineprocessingbyCD26hasasignificantimpactonphysiologicandpathologicprocesses,applicationofCD26inhibitorstoaffectchemokinefunctioniscurrentlyexplored,e.g.,asadd‐ontherapyinviralinfectionandcancer...

【 授权许可】

CC BY