Alanyl-glutamine administration suppresses Th17 and reduces inflammatory reaction in dextran sulfate sodium-induced acute colitis
Alanyl-glutamine administration suppresses Th17 and reduces inflammatory reaction in dextran sulfate sodium-induced acute colitis
复制标题
DOI：
10.1016/j.intimp.2013.05.004
复制
发表时间：
2013-09-01
影响因子：
5.6
通讯作者：
Yeh, Sung-Ling
中科院分区：
文献类型：
--
作者：
Hou, Yu-Chen;Liu, Jun-Jen;Yeh, Sung-Ling
辅助性T细胞(Th)在炎症性肠病(IBD)的发病机制中起重要作用。谷氨酰胺(Gin)在代谢应激条件下具有免疫调节作用。本研究探讨丙氨酰谷氨酰胺(Ala-Gln)对葡聚糖硫酸钠(DSS)诱导的结肠炎大鼠Th细胞相关细胞因子表达和炎症反应的影响。C57BL/6小鼠给予含3%DSS的蒸馏水连续5d诱导结肠炎，正常对照组(NC)给予蒸馏水。结肠炎模型建立后，结肠炎组(DG)腹腔注射丙氨酸-谷氨酰胺(Ala-Gln)溶液(0.5g/kg/d)，DSS组(DS)注射等量生理盐水。治疗3d后处死小鼠，采集血液和组织标本进行进一步分析。DSS结肠炎大鼠外周血中分泌IL-17的Th细胞比例增加，肠系膜淋巴结(MLN)中Th细胞相关的细胞因子信使RNA(MRNA)表达增加。此外，DS组的管腔免疫球蛋白(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组和NC组之间这些参数没有差异。DG组大鼠血中IL-17A、17F、mln IL-17mRNA及腹腔灌洗液中巨噬细胞百分率均低于DS组。这些结果提示，丙氨酸-谷氨酰胺治疗后抑制了Th17相关细胞因子的表达，减少了巨噬细胞对腹腔的侵袭，减少了结肠炎性细胞因子的产生，从而可能减轻了DSS诱导的结肠炎的炎症反应。(C)2013爱思唯尔B.V.保留所有权利。
T helper (Th) cells play a major role in the pathogenesis of inflammatory bowel disease (IBD). Glutamine (Gin) 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. (C) 2013 Elsevier B.V. All rights reserved.