Dysregulation of GABAergic Signalling Contributes in the Pathogenesis of Diarrhea-predominant Irritable Bowel Syndrome.
Dysregulation of GABAergic Signalling Contributes in the Pathogenesis of Diarrhea-predominant Irritable Bowel Syndrome.
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DOI：
10.5056/jnm17100
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发表时间：
2018-07-30
影响因子：
3.4
通讯作者：
Paul J
中科院分区：
文献类型：
--
作者：
Aggarwal S;Ahuja V;Paul J
腹泻型肠易激综合征（IBS-D）是一种常见的功能性肠病。腹痛、不适和肠道习惯改变是IBS-D的显著特征。低度炎症和神经递质改变是最近发现的导致IBS-D发病的两个因素，但它们的作用和相互作用尚未得到详细阐明。在这里，我们研究γ-氨基丁酸（GABA）在IBS-D期间调节肠道炎症的潜在作用。收集临床诊断为IBS-D的患者和对照组的血液样本和结肠粘膜活检。采用酶联免疫吸附法（ELISA）测定血清样品中GABA水平。采用逆转录聚合酶链式反应（RT-PCR）分析活检样本中gaba能系统和促炎细胞因子的表达。采用RT-PCR检测GABA及其拮抗剂对脂多糖刺激HT-29细胞促炎细胞因子表达的影响。ELISA数据显示，与对照组相比，IBS-D患者的GABA水平降低。RT-PCR分析显示，与对照组相比，IBS-D患者的gaba能信号系统发生了改变。GABA可降低LPS刺激HT-29细胞中促炎细胞因子的表达，而GABA拮抗剂双丘碱可上调LPS刺激HT-29细胞中促炎细胞因子的表达。我们的数据表明，GABA水平的降低和GABA能信号系统的改变通过调节炎症过程参与了IBS-D的发病。这些结果为GABA通过改变促炎细胞因子的表达在IBS-D患者中的抗炎作用提供了新的证据。
Diarrhea-predominant irritable bowel syndrome (IBS-D) is a prevalent functional bowel disorder. Abdominal pain, discomfort and altered intestinal habits are the salient features of IBS-D. Low grade inflammation and altered neurotransmitters are the 2 recently identified factors contributing to the pathogenesis of IBS-D, but their role and interactions has not been elucidated in detail. Here we investigate the potential role of γ-aminobutyric acid (GABA) in regulating gut inflammation during IBS-D. Blood samples and colonic mucosal biopsies from clinically diagnosed IBS-D patients and controls were collected. Levels of GABA were measured in serum samples through enzyme-linked immunosorbent assay (ELISA). Expression of GABAergic system and proinflammatory cytokines were analyzed in biopsy samples by reverse transcriptase polymerase chain reaction (RT-PCR). Effect of GABA and its antagonist on the expression of proinflammatory cytokines in lipopolysaccharide (LPS)-stimulated HT-29 cells was examined through RT-PCR. ELISA data revealed diminished level of GABA in IBS-D patients as compared to controls. RT-PCR analysis showed altered GABAergic signal system in IBS-D patients as compared to controls. GABA reduced the expression of proinflammatory cytokines in LPS stimulated HT-29 cells, whereas bicuculline methiodide (GABA antagonist) upregulated the expression of same cytokines in LPS stimulated HT-29 cells. Our sets of data indicate that diminished level of GABA and altered GABAergic signal system contributes to pathogenesis of IBS-D by regulating inflammatory processes. These results provide novel evidence for anti-inflammatory role of GABA in IBS-D patients by altering the expression of pro-inflammatory cytokines.
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影响因子：
3.6
作者：
Duthey, Beatrice;Huebner, Anita;Boehncke, Wolf-Henning
通讯作者：
Boehncke, Wolf-Henning
影响因子：
24.5
作者：
Hughes, Patrick A.;Harrington, Andrea M.;Brierley, Stuart M.
通讯作者：
Brierley, Stuart M.
DOI：
10.1152/ajpgi.00497.2011
发表时间：
2012-08-01
影响因子：
4.5
作者：
Li, Yan;Xiang, Yun-Yan;Li, Jingxin
通讯作者：
Li, Jingxin
影响因子：
3
作者：
Nigam, Rishi;El-Nour, Husameldin;Nordlind, Klas
通讯作者：
Nordlind, Klas
DOI：
10.1073/pnas.0915139107
发表时间：
2010-02-09
影响因子：
11.1
作者：
Bhat, Roopa;Axtell, Robert;Steinman, Lawrence
通讯作者：
Steinman, Lawrence