Evans BioMedical Research Center, Section of Infectious Diseases, Department of Medicine, Boston University School of Medicine, Rm. 635, 650 Albany Street, Boston, MA 02118, USA.
Infect Immun. 2010 Mar;78(3):994-1003. doi: 10.1128/IAI.00156-09. Epub 2009 Dec 22.
Meningococcal porin PorB is an inhibitor of apoptosis induced via the intrinsic pathway in various cell types. This effect is attributed to prevention of mitochondrial depolarization and of subsequent release of proapoptotic mitochondrial factors. To determine whether apoptosis is globally inhibited by PorB, we compared the intrinsic and extrinsic pathways in HeLa cells. Interestingly, PorB does not prevent extrinsic apoptosis induced by tumor necrosis factor alpha plus cycloheximide, suggesting a unique mitochondrial pathway specificity. Several intracellular factors regulated by NF-kappaB, including members of the Bcl-2 family and of the inhibitor of apoptosis (IAP) family, play major roles in controlling apoptosis, and some of them are thought to contribute to the antiapoptotic effect of the gonococcal porin, PIB. However, most of the members of the Bcl-2 family and the IAP family are not induced by meningococcal PorB in HeLa cells, with the exception of Bfl-1/A1. Interestingly, PorB does not induce NF-kappaB activation in HeLa cells, likely due to a lack of Toll-like receptor 2 (TLR2) expression in these cells. Bfl-1/A1 expression is also regulated by CBF1, a nuclear component of the Notch signaling pathway, independent of NF-kappaB activation. Since HeLa cells are protected by PorB from intrinsic apoptosis events, regardless of TLR2 and NF-kappaB expression, the possibility of a contribution of alternative signaling pathways to this effect cannot be excluded. In this paper, we describe an initial dissection of the cascade of cellular events involved in the antiapoptotic effect of PorB in the absence of TLR2.
脑膜炎球菌外膜孔蛋白 PorB 可抑制多种细胞类型中通过内在途径诱导的细胞凋亡。这种作用归因于阻止线粒体去极化和随后促凋亡的线粒体因子的释放。为了确定 PorB 是否全局抑制细胞凋亡，我们比较了 HeLa 细胞中的内在和外在途径。有趣的是，PorB 不能阻止肿瘤坏死因子-α加环己酰亚胺诱导的外在凋亡，这表明其具有独特的线粒体途径特异性。许多受 NF-κB 调控的细胞内因子，包括 Bcl-2 家族和凋亡抑制蛋白（IAP）家族的成员，在控制凋亡中发挥主要作用，其中一些被认为有助于淋球菌外膜孔蛋白 PIB 的抗凋亡作用。然而，在 HeLa 细胞中，除了 Bfl-1/A1 外，脑膜炎球菌 PorB 并不诱导大多数 Bcl-2 家族和 IAP 家族成员的表达，除了 Bfl-1/A1。有趣的是，PorB 不会诱导 HeLa 细胞中的 NF-κB 激活，这可能是由于这些细胞中缺乏 Toll 样受体 2（TLR2）的表达。Bfl-1/A1 的表达也受 CBF1 调控，CBF1 是 Notch 信号通路的核成分，与 NF-κB 激活无关。由于 PorB 可保护 HeLa 细胞免受内在凋亡事件的影响，无论 TLR2 和 NF-κB 的表达如何，都不能排除替代信号通路对这种作用的贡献。在本文中，我们描述了在缺乏 TLR2 的情况下，PorB 抗凋亡作用涉及的细胞事件级联的初步剖析。
