Apoptotic Pathways in Pemphigus英文文献资料.docVIP

HindawiPublishingCorporation DermatologyResearchandPractice Volume2010,ArticleID456841,8pages doi:10.1155/2010/456841 ReviewArticle ApoptoticPathwaysinPemphigus MeryemBektas, PuneetJolly, 1 1andDavidS.Rubenstein1,2,3 1 2 3 DepartmentofDermatology,UniversityofNorthCarolina-ChapelHillSchoolofMedicine,ChapelHill,NC27599,USA DepartmentofPharmacology,UniversityofNorthCarolina-ChapelHillSchoolofMedicine,ChapelHill,NC27599,USA LinebergerComprehensiveCancerCenter,UniversityofNorthCarolina-ChapelHillSchoolofMedicine,ChapelHill, NC27599,USA CorrespondenceshouldbeaddressedtoDavidS.Rubenstein,druben@ Received14December2009;Accepted24February2010 AcademicEditor:M?yG.Mahoney Copyright?2010MeryemBektasetal. This is an open access article distributed under the Creative Commons Attribution License,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperly cited. Pemphigusisagroupofhumanautoimmuneblisteringdiseasesoftheskininwhichautoantibodiestodesmosomecadherins inducelossofcell-celladhesion(acantholysis).Inadditiontosterichindranceandactivationofintracellularsignaling,apoptosis hasbeensuggestedtocontributetothemechanismbywhichpathogenicIgGinducesacantholysis.Wereviewthecurrentliterature examining the role of apoptosis in pemphigus. Current data suggest that apoptosis is not required for blister induction, but thatactivationofproapoptoticproteins,includingcaspasecysteineproteinases,maysensitizecellstotheacantholytice?ectsof pemphigusIgG. 1.Introduction cell-cell adhesion. The observation that pemphigus IgG weredirectedagainstthedesmosomalcadherinsdsg-1and dsg-3 led to the suggestion that the IgG inhibited trans interactions of desmosome adhesion proteins across the adhesiveinterface,amechanismknowasthesterichindrance hypothesis. Alternative hypotheses have been suggested, includingantibodyinductionofintracellularsignalingthat leads to loss of adhesion, and antibody induction of ker- atinocyteapoptosis. Changesincell-cellad