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• W4313376988 endingPage "6131" @default.
• W4313376988 startingPage "6122" @default.
• W4313376988 abstract "Abstract The Bcg/Nramp1 gene controls early resistance and susceptibility of macrophages to mycobacterial infections. We previously reported that Mycobacterium tuberculosis-infected (Mtb) B10R (Bcgr) and B10S (Bcgs) macrophages differentially produce nitric oxide (NO−), leading to macrophage apoptosis. Since TNF-α and IL-10 have opposite effects on many macrophage functions, we determined the number of cells producing TNF-α and IL-10 in Mtb-infected or purified protein derivative-stimulated B10R and B10S macrophages lines, and Nramp1+/+ and Nramp1−/− peritoneal macrophages and correlated them with Mtb-mediated apoptosis. Mtb infection and purified protein derivative treatment induced more TNF-α+Nramp1+/+ and B10R, and more IL-10+Nramp1−/− and B10S cells. Treatment with mannosylated lipoarabinomannan, which rescues macrophages from Mtb-induced apoptosis, augmented the number of IL-10 B10R+ cells. Anti-TNF-α inhibited apoptosis, diminished NO− production, p53, and caspase 1 activation and increased Bcl-2 expression. In contrast, anti-IL-10 increased caspase 1 activation, p53 expression, and apoptosis, although there was no increment in NO− production. Murine rTNF-α induced apoptosis in noninfected B10R and B10S macrophages that was reversed by murine rIL-10 in a dose-dependent manner with concomitant inhibition of NO− production and caspase 1 activation. NO− and caspase 1 seem to be independently activated in that aminoguanidine did not affect caspase 1 activation and the inhibitor of caspase 1, Tyr-Val-Ala-Asp-acylooxymethylketone, did not block NO− production; however, both treatments inhibited apoptosis. These results show that Mtb activates TNF-α- and IL-10-dependent opposite signals in the induction of macrophage apoptosis and suggest that the TNF-α-IL-10 ratio is controlled by the Nramp1 background of resistance/susceptibility and may account for the balance between apoptosis and macrophage survival." @default.
• W4313376988 created "2023-01-06" @default.
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• W4313376988 creator A5047989235 @default.
• W4313376988 date "1999-05-15" @default.
• W4313376988 modified "2023-10-17" @default.
• W4313376988 title "TNF-α and IL-10 Modulate the Induction of Apoptosis by Virulent <i>Mycobacterium tuberculosis</i> in Murine Macrophages" @default.
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• W4313376988 doi "https://doi.org/10.4049/jimmunol.162.10.6122" @default.
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