Team: Cytokines and NOSynthases, Laboratory of Cellular and Molecular Biology (LBCM), Faculty of Biological Science, USTHB, Algiers, Algeria.
J Interferon Cytokine Res. 2010 Sep;30(9):691-7. doi: 10.1089/jir.2010.0012.
The pathogenesis of inflammatory bowel disease (IBD) is complex, involving a wide range of molecules including cytokines. Abnormalities in the expression of immunoregulatory cytokines such as interferon-γ (IFN-γ) and interleukin-12 (IL-12) may indicate a dysregulation of intestinal immunity probably associated with pathogenic events. The aim of this work was to study the implication of IFN-γ and nitric oxide (NO) in bowel disease pathogenesis. In this study, we investigated the circulating IFN-γ and IL-12 production in 2 groups of Algerian patients with IBD (Crohn's disease and ulcerative colitis). Moreover, systemic NO concentrations and NO generation by colonic mucosa were determined in these patients. Finally, we examined the effect of IFN-γ on NO production by peripheral blood mononuclear cells (PBMCs) of these patients. Our results indicate that IFN-γ/IL-12 production in IBD patients was increased in comparison to healthy donors. This strong production correlates with high levels of NO in sera and colonic mucosa culture. Interestingly, NO production was related to the clinical stage of IBD patients (inactive or active stage). The relationship between IFN-γ and NO production in IBD patients were confirmed by in vitro experiments and the role of IFN-γ in NO synthase induction in patients' PBMC culture was suggested. Collectively, our results show that IFN-γ plays a pivotal role in IBD pathogenesis through NO pathway.
炎症性肠病（IBD）的发病机制复杂，涉及多种分子，包括细胞因子。免疫调节细胞因子如干扰素-γ（IFN-γ）和白细胞介素-12（IL-12）的表达异常可能表明肠道免疫失调，可能与致病事件有关。本工作旨在研究 IFN-γ和一氧化氮（NO）在肠病发病机制中的作用。在这项研究中，我们研究了两组来自阿尔及利亚的 IBD（克罗恩病和溃疡性结肠炎）患者的循环 IFN-γ和 IL-12 产生情况。此外，我们还测定了这些患者的全身 NO 浓度和结肠黏膜的 NO 生成。最后，我们检查了 IFN-γ对这些患者外周血单核细胞（PBMC）NO 生成的影响。我们的结果表明，与健康供体相比，IBD 患者的 IFN-γ/IL-12 产生增加。这种强烈的产生与血清和结肠黏膜培养物中高水平的 NO 相关。有趣的是，NO 生成与 IBD 患者的临床分期（活动期或缓解期）有关。在体外实验中证实了 IBD 患者中 IFN-γ 和 NO 产生之间的关系，并提示 IFN-γ在患者 PBMC 培养物中诱导一氧化氮合酶中的作用。总之，我们的研究结果表明，IFN-γ 通过 NO 途径在 IBD 发病机制中起关键作用。
