L-cysteine supplementation attenuates local inflammation and restores gut homeostasis in a porcine model of colitis
L-cysteine supplementation attenuates local inflammation and restores gut homeostasis in a porcine model of colitis
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DOI：
10.1016/j.bbagen.2009.05.018
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发表时间：
2009-10-01
影响因子：
3
通讯作者：
Mine, Y.
中科院分区：
文献类型：
--
作者：
Kim, C. J.;Kovacs-Nolan, J.;Mine, Y.
背景：炎症性肠病 (IBD) 是一种胃肠道慢性炎症，其特征是粘膜免疫系统失调和活化 T 细胞对凋亡的抵抗。目前的治疗方法显示出有限的功效和潜在的毒性；因此，需要治疗IBD的新方法。在 DSS 诱导的猪结肠炎模型中，检查了 L-半胱氨酸减轻结肠炎症状和调节局部基因表达的能力。方法：通过胃内输注右旋糖酐硫酸钠 (DSS)，然后给予 L-半胱氨酸或盐水来诱导结肠炎。评估临床体征、形态学测量、组织学和肠道通透性以评估结肠炎的预后。通过 ELISA 和实时 RT-PCR 分析结肠中细胞因子的局部组织产生和基因表达。结果：L-半胱氨酸补充剂减弱了 DSS 引起的体重减轻和肠道通透性，减少了局部趋化因子表达和中性粒细胞流入，并显着改善了结肠组织学。此外，半胱氨酸显着降低促炎细胞因子的表达，包括 TNF-α、IL-6、IL-12p40、IL-1β，并导致凋亡启动子 caspase-8 的表达增加，促生存基因 cFLIP 和 Bcl-xL 的表达减少。结论和一般意义：这些结果表明，L-半胱氨酸给药有助于通过减弱炎症反应和恢复易感性来恢复肠道免疫稳态。激活的免疫细胞凋亡，补充半胱氨酸可能是治疗 IBD 的一种新的治疗策略。 (C) 2009 Elsevier B.V. 保留所有权利。
Background: Inflammatory bowel disease (IBD), a chronic inflammation of the gastrointestinal tract, is characterized by a deregulation of the mucosal immune system and resistance of activated T cells to apoptosis. Current therapeutics show limited efficacy and potential toxicity; therefore there is a need for novel approaches for the treatment of IBD. L-cysteine was examined for its ability to reduce colitis symptoms and modulate local gene expression in a DSS-induced porcine model of colitis.Methods: Colitis was induced via intra-gastric infusion of dextran sodium sulfate (DSS), followed by the administration of L-cysteine or saline. Clinical signs, morphological measurements, histology and gut permeability were assessed for the prognosis of colitis. Local tissue production of cytokines and gene expression in the colon were analyzed by ELISA and real-time RT-PCR.Results: L-cysteine supplementation attenuated DSS-induced weight loss and intestinal permeability, reduced local chemokine expression and neutrophil influx, and markedly improved colon histology. Furthermore, cysteine significantly reduced the expression of pro-inflammatory cytokines, including TNF-alpha, IL-6, IL-12p40, IL-1 beta, and resulted in increased expression of the apoptosis initiator caspase-8 and decreased expression of the pro-survival genes cFLIP and Bcl-xL.Conclusions and general significance: These results suggest that L-cysteine administration aids in restoring gut immune homeostasis by attenuating inflammatory responses and restoring susceptibility of activated immune cells to apoptosis, and that cysteine supplementation may be a novel therapeutic strategy for the treatment of IBD. (C) 2009 Elsevier B.V. All rights reserved.