Meningococcal porin PorB prevents cellular apoptosis in a toll-like receptor 2- and NF-kappaB-independent manner.
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.
Massari
Paola
P
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. pmassari@bu.edu
Gunawardana
Jay
J
Liu
Xiuping
X
Wetzler
Lee M
LM
D017209:Apoptosis; D004847:Epithelial Cells / Q000382:microbiology; D006367:HeLa Cells; D006801:Humans; D016328:NF-kappa B / Q000276:immunology*; D009345:Neisseria meningitidis / Q000276:immunology* / Q000472:pathogenicity*; D018272:Porins / Q000502:physiology*; D051195:Toll-Like Receptor 2 / Q000276:immunology*; D037521:Virulence Factors / Q000502:physiology*
D016328:NF-kappa B; D018272:Porins; D051195:Toll-Like Receptor 2; D037521:Virulence Factors; C057699:porin protein, Neisseria