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精氨酸-谷氨酰胺给药可抑制白细胞介素-17,减轻葡聚糖硫酸钠诱导的急性结肠炎的炎症反应。

Alanyl-glutamine administration suppresses Th17 and reduces inflammatory reaction in dextran sulfate sodium-induced acute colitis.

机构信息

School of Nutrition and Health Sciences, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan.

出版信息

Int Immunopharmacol. 2013 Sep;17(1):1-8. doi: 10.1016/j.intimp.2013.05.004. Epub 2013 May 27.

DOI:10.1016/j.intimp.2013.05.004
PMID:23721689
Abstract

T helper (Th) cells play a major role in the pathogenesis of inflammatory bowel disease (IBD). Glutamine (Gln) is known to have immunomodulatory effects in metabolic stressed conditions. This study investigated the effects of post-treatment of alanyl-glutamine (Ala-Gln) on Th cell-associated cytokine expressions and inflammatory reaction in dextran sulfate sodium (DSS)-induced colitis. C57BL/6 mice received distilled water containing 3% DSS for 5 days to induce colitis, whereas the normal control (NC) group received distilled water. After induction of colitis, one of the colitis groups (DG) was intraperitoneally injected with an Ala-Gln solution (0.5 g Gln/kg/d), and the saline DSS group (DS) received an identical volume of saline. After treatment for 3 days, mice were sacrificed, and the blood and tissue samples were collected for further analysis. DSS colitis resulted in higher percentages of blood interleukin (IL)-17-secreting Th cells and greater expression of Th cell-associated cytokine messenger RNA (mRNA) in the mesenteric lymph nodes (MLN). Also, luminal immunoglobin (Ig) G, keratinocyte-derived chemokine, and macrophage chemoattractant protein-1 levels were higher in the DS group than the NC group, whereas these parameters did not differ between the DG and NC groups. The DG group had lower blood IL-17A, 17F, MLN IL-17 mRNA and macrophage percentage in the peritoneal lavage fluid than those of the DS group. These results suggest that post-treatment with Ala-Gln suppressed Th17-associated cytokine expressions, reduced macrophage infiltration into the peritoneal cavity and decreased pro-inflammatory cytokine production in the colon, thus may have attenuated inflammatory response in DSS-induced colitis.

摘要

辅助性 T 细胞(Th)在炎症性肠病(IBD)的发病机制中起主要作用。谷氨酰胺(Gln)在代谢应激状态下具有免疫调节作用。本研究探讨了术后给予丙氨酰-谷氨酰胺(Ala-Gln)对葡聚糖硫酸钠(DSS)诱导结肠炎中 Th 细胞相关细胞因子表达和炎症反应的影响。C57BL/6 小鼠接受含 3% DSS 的蒸馏水 5 天以诱导结肠炎,而正常对照组(NC)接受蒸馏水。诱导结肠炎后,将结肠炎组之一(DG)腹腔内注射 Ala-Gln 溶液(0.5g Gln/kg/d),而盐水 DSS 组(DS)接受相同体积的盐水。治疗 3 天后,处死小鼠,采集血液和组织样本进行进一步分析。DSS 结肠炎导致肠系膜淋巴结(MLN)中血液白细胞介素(IL)-17 分泌 Th 细胞的百分比更高,Th 细胞相关细胞因子信使 RNA(mRNA)的表达更高。此外,DS 组的腔免疫球蛋白(Ig)G、角质形成细胞衍生趋化因子和巨噬细胞趋化蛋白-1 水平高于 NC 组,而 DG 组与 NC 组之间这些参数没有差异。DG 组的血液 IL-17A、17F、MLN IL-17mRNA 和腹腔灌洗液中的巨噬细胞百分比低于 DS 组。这些结果表明,术后给予 Ala-Gln 可抑制 Th17 相关细胞因子表达,减少巨噬细胞浸润腹腔和减少结肠中促炎细胞因子的产生,从而可能减轻 DSS 诱导的结肠炎中的炎症反应。

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