Modulation of IL-12 by transforming growth factor-beta (TGF-beta) in Mycobacterium tuberculosis-infected mononuclear phagocytes and in patients with active tuberculosis.

Z Toossi, M Mincek, E Seeholtzer, S A Fulton, B D Hamilton, C S Hirsch
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Abstract

In humans, tuberculosis is associated with suppression of T-cell responses to antigens of Mycobacterium tuberculosis. Recently, the macrophage product, transforming growth factor-beta (TGF-beta) has been implicated in suppression of T-cell proliferation and cytokine production during tuberculosis. We studied the effect of TGF-beta on production of IL-12, and on the augmentation of M. tuberculosis-induced IFN gamma production by IL-12, in patients with pulmonary tuberculosis and by M. tuberculosis. Induction of IL-12 p35, but not IL-12 p40, by M. tuberculosis in monocytes was dependent on prior priming of the cells with IFN gamma. Expression of both IL-12 p40 and p35, however, was suppressed by TGF-beta. Further, TGF-beta interfered with the bioactivity of IL-12 in the enhancement of M. tuberculosis-induced IFN gamma mRNA expression and cytokine production. However, in mononuclear cells from patients with tuberculosis the main effect of TGF-beta on IL-12 appeared to be counter action to IL-12 induced IFN gamma production in response to M. tuberculosis.

转化生长因子- β (tgf - β)在结核分枝杆菌感染的单核吞噬细胞和活动性结核患者中对IL-12的调节
在人类中,结核病与抑制t细胞对结核分枝杆菌抗原的反应有关。最近,巨噬细胞产物转化生长因子- β (tgf - β)被认为与结核期间t细胞增殖和细胞因子产生的抑制有关。我们在肺结核患者和结核分枝杆菌中研究了tgf - β对IL-12产生的影响,以及IL-12对结核分枝杆菌诱导的IFN γ产生的增强作用。结核分枝杆菌在单核细胞中诱导il - 12p35,而不是il - 12p40,依赖于先前用IFN γ启动细胞。然而,IL-12 p40和p35的表达均被tgf - β抑制。此外,tgf - β干扰IL-12的生物活性,增强结核分枝杆菌诱导的IFN γ mRNA表达和细胞因子的产生。然而,在结核患者的单核细胞中,tgf - β对IL-12的主要作用似乎是对抗IL-12诱导的IFN γ产生,以应对结核分枝杆菌。
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