简介:树枝状的房间(DC)在造血的房间的一张次要的人口,生产类型我干扰素(IFN)和另外的cytokines并且为天生的免疫是必要的。他们也是有势力抗原演讲者并且调整适应免疫。在DC子类型血浆之中似细胞的DC(pDC)生产类型的最高的数量我IFN。另外,象IL-12和IL-10那样的支持inflammatory和反煽动性的cytokines响应象发信号的受体(TLR)一样并且在病毒的感染之上的代价在DC被导致。在IRF家庭的蛋白质控制DC活动的许多方面。IRF-8和IRF-4为DC开发是必要的。他们差别控制四个DC子集的开发。IRF-8-/-老鼠大部分缺乏pDC和CD8alpha+DC,当IRF-4-/-老鼠缺乏CD4+DC时。IRF-8-/-,IRF4-/-,两倍猛烈老鼠有仅仅很少CD8a-CD4-DC那缺乏MHCII。IRF蛋白质也控制类型我在DC的IFN正式就职。IRF-7,在TLR发信号之上激活不仅在pDC,而且在常规DC(cDC)为IFN正式就职被要求,non-DC房间打字。IRF-3贡献在成纤维细胞感应的IFN,在在DC感应的IFN是非必需的。我们的最近的证据揭示那种类型我在DC感应的IFN非常依赖于IRF-8,它在DC在IFN基因正式就职的反馈阶段行动。类型我在pDC感应的IFN被MyD88调停依赖发信号小径,并且不同于在另外的房间采用的小径,它主要依靠TLR3和RIG-I家庭蛋白质。另外的支持inflammatorycytokines以一种IRF-5依赖方式被生产。然而,IRF-5没为IFN正式就职被要求,建议为类型的正式就职的分开的机制的存在我IFN和其它支持inflammatorycytokines。激活的DC接着生产的IFN和另外的cytokines预付DC成熟并且改变DC的显型和功能。这些过程也是可能的被IRF家庭蛋白质管理。
简介:AktandBcl-xLbothpromoteresistancetoapoptosis.AcomparisonofAkt-andBcl-xL-dependentcellsurvivalwasundertaken.ExpressionofconstitutivelyactiveAktallowscellstosurviveforprolongedperiodsintheabsenceofgrowthfactors.ThissurvivalcorrelateswiththeexpressionlevelofactivatedAktandiscomparableinmagnitudetotheprotectionprovidedbytheanti-apoptoticgeneBcl-xL.Althoughbothgenespreventcelldeath,Akt-protectedcellscanbedistinguishedfromBcl-xL-protectedcellsonthebasisofincreasedglucosetransporterexpression,glycolyticactivity,mitochondrialpotential,andcellsize.Inaddition,Akt-expressingcellsrequirehighlevelsofextracellularnutrientstosupportcellsurvival.In
简介:ThesplicingofmanyalternativeexonsintheprecursormessengerRNA(pre-mRNA)isregulatedbyextracellularfactorsbuttheunderlyingmolecularbasesremainunclear.HerewereportthedifferentialregulationofBcl-xpre-mRNAsplicingbyextracellularfactorsandtheirdistinctrequirementsforpre-mRNAelements.InK562leukemiacells,treatmentwithinterleukin-6(IL-6)orgranulocyte-macrophagecolonystimulatingfactor(GM-CSF)reducedtheproportionoftheBcl-xLvariantmRNAwhiletreatmentwith12-O-tetradecanoylphorbol13-acetate(TPA)hadnoeffect.InU251gliomacells,however,TPAefficientlyincreasedtheBcl-xLlevel.Theseregulationswerealsoseenforatransfectedsplicingreportermini-gene.Furtheranalysesofdeletionmutantsindicatethatnucleotides1-176ofthedownstreamintronarerequiredfortheIL-6effect,whereasadditionalnucleotides177-284areessentialfortheGM-CSFeffect.AsfortheTPAeffect,onlynucleotides1-76arerequiredinthedownstreamintron.Thus,IL-6,GM-CSFandTPAdifferentiallyregulateBcl-xsplicingandrequirespecificintronicpre-mRNAsequencesfortheirrespectiveeffects.