کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2401839 1102375 2009 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Suppression of IFNγ + mycobacterial lipoarabinomannan-induced NO by IL-4 is due to decreased IRF-1 expression
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی میکروبیولوژی و بیوتکنولوژی کاربردی
پیش نمایش صفحه اول مقاله
Suppression of IFNγ + mycobacterial lipoarabinomannan-induced NO by IL-4 is due to decreased IRF-1 expression
چکیده انگلیسی

SummaryIn mice, and possibly in humans, nitric oxide (NO) is an important host-defense molecule against Mycobacterium tuberculosis. Inducible nitric oxide synthase (iNOS) and NO are upregulated in murine macrophages stimulated with interferon-gamma (IFNγ) and mannose-capped lipoarabinomannan (ManLAM), a major lipoglycan in the cell wall of M. tuberculosis. Interleukin-4 (IL-4) can inhibit NO expression and may impair host immune response to M. tuberculosis. Therefore, we sought to determine the mechanism by which IL-4 inhibits IFNγ + ManLAM-induced NO production. Since l-arginine is the substrate for both iNOS and arginase, and IL-4 increases arginase activity by inducing its production, a plausible mechanism of IL-4 inhibition of NO expression is via depletion of l-arginine through increased arginase activity. Herein, we show that IL-4 inhibited iNOS gene expression at the transcriptional level, suggesting an inhibitory mechanism that is independent of the competition for l-arginine between iNOS and arginase. Furthermore, pharmacologic inhibition of IL-4-induced arginase activity did not abrogate IL-4 inhibition of IFNγ + ManLAM-induced NO expression. Instead, inhibition by IL-4 was mediated principally by the ability of IL-4 to inhibit the production of IFNγ-induced interferon-gamma response factor-1 (IRF-1) protein, a critically important transcriptional element that enhances expression of IFNγ-inducible genes such as iNOS.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Tuberculosis - Volume 89, Issue 4, July 2009, Pages 294–303
نویسندگان
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