Institute of Biochemistry, University of Nis, Serbia.
Redox Rep. 2010;15(4):179-84. doi: 10.1179/174329210X12650506623564.
A high prevalence of various infectious diseases is reported in diabetic patients, which may suggest impaired innate immunity against different pathogen-associated molecular patterns. This study investigated the effects of hyperglycemia, oxidative stress (H(2)O(2)), nitric oxide (NO) and peroxynitrite (ONOO(-)) on the modulation of antiviral (MDA-5, IRF-3 and phospho-IRF-3), inflammatory (NF-kappaB) and pro/anti-apoptotic molecules (Bax and Bcl-2) in BALB/c mice thymocytes. Each of the experimental conditions, except the weakest NO concentration, resulted in down-regulation of MDA-5, IRF-3 and phospho-IRF-3. In contrast, each of the experimental conditions elicited up-regulation of NF-kappaB, Bcl-2 and Bax. These results suggest that hyperglycemia, oxidative and nitrosative stress may contribute to the reduced immunity of the host by altering the MDA-5/IRF-3/phosphoIRF-3 axis, as well as contributing to the mechanisms of inflammatory reaction via increased NF-kappaB, and to augmented turnover rate of thymocyte cells via Bcl2/Bax up-regulation.
糖尿病患者常患有各种传染病，这表明他们对不同病原体相关分子模式的固有免疫受损。本研究探讨了高血糖、氧化应激（H₂O₂）、一氧化氮（NO）和过氧亚硝酸盐（ONOO⁻）对 BALB/c 小鼠胸腺细胞抗病毒（MDA-5、IRF-3 和磷酸化-IRF-3）、炎症（NF-κB）和促凋亡/抗凋亡分子（Bax 和 Bcl-2）调节的影响。除了最弱的 NO 浓度外，每种实验条件都导致 MDA-5、IRF-3 和磷酸化-IRF-3 的下调。相比之下，每种实验条件都引起 NF-κB、Bcl-2 和 Bax 的上调。这些结果表明，高血糖、氧化和硝化应激可能通过改变 MDA-5/IRF-3/磷酸化-IRF-3 轴，以及通过增加 NF-κB 促进炎症反应机制，并通过上调 Bcl2/Bax 增加胸腺细胞细胞的更新率，从而导致宿主免疫力下降。
