The role of the Src family kinase Lyn in the immunomodulatory activities of cathelicidin peptide LL‐37 on monocytic cells

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

关键词: monocyte;    chemokine;    signaling pathways;   

DOI  :  10.1189/jlb.0411191

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

CathelicidinLL‐37isamultifunctional,immunomodulatoryandantimicrobialhost‐defensepeptideofthehumanimmunesystem.Here,weidentifiedtheroleofSFKsinmediatingthechemokineinductionactivityofLL‐37inmonocyticcells.LL‐37inducedSFKphosphorylation;andchemicalinhibitorsofSFKssuppressedchemokineproductioninresponsetoLL‐37stimulation.SFKswererequiredforthedownstreamactivationofAKT,butCa2+‐fluxandMAPKinductionwereSFK‐independent.ThroughsystematicsiRNAknockdownofSFKmembers,arequirementforLyninmediatingLL‐37activitywasidentified.TheinvolvementofLynincathelicidinactivitieswasfurtherconfirmedusingLyn‐knockoutmouseBMDMs.TheroleofSFKsandLynwasalsodemonstratedintheactivitiesofthesyntheticcationicIDRpeptides,developedasnovel,immunomodulatorytherapeutics.ThesefindingselucidatethecommonmolecularmechanismsmediatingthechemokineinductionactivityofnaturalandsyntheticcationicpeptidesinmonocyticcellsandidentifySFKsasapotentialtargetformodulatingpeptideresponses...

【 授权许可】

CC BY