Faculté des Sciences Biologiques, Laboratoire de Biologie Cellulaire et Moléculaire, Université des Sciences et de la Technologie Houari Boumediene, Alger, Algeria.
Int Immunopharmacol. 2012 Jan;12(1):302-11. doi: 10.1016/j.intimp.2011.10.010. Epub 2011 Oct 29.
The up regulation of gut mucosal cytokines such as tumor necrosis factor (TNF)-α and oxidative stress have been related to inflammatory bowel diseases (IBD) such as ulcerative colitis (UC) and Crohn's disease (CD). This study investigated an immune-mediated model of colitis. TNF-α injected intraperitonally to mice induced a dose-dependent recruitment of neutrophils into abdominal mesentery. The leukocytes influx induced by TNF-α (10 μg kg(-1) body weight) increased by 3 fold liver and colon damage scores. TNF-α-colitis was characterized by hemorrhagic edemas and crypt abscesses massively infiltrated by inflammatory cells, namely neutrophils. Moreover, TNF-α-toxicity resulted in liver steatosis and foci of necrosis infiltrated by Kupffer cells and neutrophils in parenchyma and around the centrilobular veins. The involvement of oxidative stress was evaluated using aminoguanidine (AG) as selective inhibitor of inducible NO synthase (iNOS) and curcumin (Cur), the polyphenolic antioxidant of turmeric (Curcuma longa L.). TNF-α-toxicity led to significant increase in myeloperoxidase (MPO, an index of neutrophils infiltration), nitrites (stable nitric oxide metabolites) and malondialdehyde (MDA, a marker of lipid peroxides) levels and cell apoptosis in liver and colon. AG and Cur treatments significantly attenuated the hallmarks of oxidative stress, neutrophils influx and ROS-related cellular and histological damages, in TNF-α-treated mice. Taken together, our results provide insights into the role of phagocytes-derived oxidants in TNF-α-colitis in mice. Cur and AG, by inhibiting neutrophils priming and iNOsynthase could be effective against oxidative bowel damages induced in IBD by imbalanced gut immune response.
肠道黏膜细胞因子（如肿瘤坏死因子（TNF）-α）的上调和氧化应激与炎症性肠病（IBD）如溃疡性结肠炎（UC）和克罗恩病（CD）有关。本研究调查了一种结肠炎的免疫介导模型。TNF-α腹腔内注射到小鼠中，诱导中性粒细胞在腹部肠系膜中的剂量依赖性募集。TNF-α（10 μg kg（-1）体重）诱导的白细胞流入使肝和结肠损伤评分增加了 3 倍。TNF-α-结肠炎的特征是出血性水肿和隐窝脓肿大量浸润炎症细胞，即中性粒细胞。此外，TNF-α毒性导致肝脏脂肪变性和坏死灶，其中浸润了库普弗细胞和中性粒细胞，位于肝实质和中央静脉周围。氧化应激的参与通过氨基胍（AG）作为诱导型一氧化氮合酶（iNOS）的选择性抑制剂和姜黄素（Cur），姜黄（Curcuma longa L.）的多酚抗氧化剂来评估。TNF-α毒性导致肝和结肠中髓过氧化物酶（MPO，中性粒细胞浸润的指标）、亚硝酸盐（稳定的一氧化氮代谢物）和丙二醛（MDA，脂质过氧化物的标志物）水平以及细胞凋亡显著增加。AG 和 Cur 处理显著减轻了 TNF-α处理小鼠中氧化应激、中性粒细胞流入和 ROS 相关的细胞和组织损伤的特征。总之，我们的结果提供了吞噬细胞衍生的氧化剂在 TNF-α-结肠炎中作用的见解。Cur 和 AG 通过抑制中性粒细胞的启动和 iNOS 可能对由肠道免疫反应失衡引起的 IBD 中的氧化肠损伤有效。
