Heat shock proteins and high mobility group box 1 protein lack cytokine function

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

关键词: danger signals;    endogenous ligands of TLRs;    alarmins;    damage‐;    associated molecules;    pathogen‐;    associated molecules;   

DOI  :  10.1189/jlb.0810471

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Insearchoftheetiologyandpathophysiologyforautoimmuneandchronicinflammatorydiseases,manymoleculeshavebeenidentifiedasendogenousdamage‐associatedmoleculeswithproinflammatorycytokinefunctionsthatmayberesponsibleforthesterileinflammationleadingtotissueinjuriesobservedinthesedisorders.HSPsandHMGB1areintracellularmolecularchaperonesforpeptidesandDNAs,respectively.Theyarereleasedextracellularlyuponcellularinjuryoractivation.InvitrostudiesrevealedthatHSPsandHMGB1werecapableofinducingthereleaseofproinflammatorycytokinesbymonocytesandmacrophagesandtheactivationandmaturationofDCs.ThesecytokineeffectswerereportedtobemediatedbyTLR2andTLR4signaltransductionpathways.Thus,theywerecalledendogenousligandsofTLR2andTLR4andmightserveasdangersignals,alarmins,ordamage‐associatedmoleculestothehostimmunesystem.IthasbeensuggestedthatHSPsprovidealinkbetweeninnateandadaptiveimmunesystems,andHMGB1functionsatthecross‐roadbetweeninnateandadaptiveimmunity.However,recentevidencesuggeststhathighlypurifiedHSPsandHMGB1,althoughretainingtheirbiologicalactivities,donothavecytokineeffects.Thus,HSPsandHMGB1donotmeetthedefinitionofendogenousligandsofTLRs,dangersignals,alarmins,ordamage‐associatedmolecules.Incontrast,HSPsandHMGB1arefoundtobindanumberofpathogen‐associatedmolecules,suchasLPSandbacteriallipopeptides,andenhancethecytokineeffectsofthesemolecules.Thesignificanceofthesecytokine‐enhancingeffectsofHSPsandHMGB1needsfurtherinvestigation...

【 授权许可】

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