Activation of GABAA Receptors in Colon Epithelium Exacerbates Acute Colitis

Frontiers in Immunology

Chuanfei Wei¹  Xiaotong Sun²  Yanqing Li³  Qian Sun⁴  Xuelian Ma⁴  Jingxin Li⁴  Xin Yu⁴  Chuanyong Liu⁴  Dawei Chen⁵ 

[1] Centre for Stem Cell and Regenerative Medicine, Liaocheng People’s Hospital, Liaocheng, China;Department of Anesthesiology, Qilu Hospital, Shandong University, Jinan, China;Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, China;Department of Physiology, School of Basic Medical Sciences, Shandong University, Jinan, China;Laboratory of Medical Chemistry, GIGA-Molecular Biology of Diseases, Faculty of Medicine, University of Liège, Liège, Belgium;

关键词: gamma-aminobutyric acid;    ulcerative colitis;    mucosal barrier;    epithelial proliferation;    apoptosis;   

DOI  :  10.3389/fimmu.2018.00987

来源: DOAJ

【 摘 要 】

Emerging evidence indicates that gamma-aminobutyric acid (GABA) has many beneficial effects such as ameliorating immune and inflammatory response. But, here we reported that activation of GABAA receptors (GABAA Rs) aggravated dextran sulfate sodium (DSS)-induced colitis, although the expression of pro-inflammatory cytokines was inhibited. By contrast, blocking of GABAA Rs markedly alleviated DSS-induced colitis. Notably, GABAA Rs and glutamic acid decarboxylase 65/67 were significantly increased in colon mucosa of ulcerative colitis patients and the mouse model of colitis. Further studies showed that GABA treatment resulted in an increment of serum FITC-dextran following its oral administration, a decrement of transepithelial electrical resistance, and an increment of bacterial invasion, effects which were blocked by bicuculline. In addition, GABA inhibited the expression of tight junction proteins and mucin secretion in colitis colon. GABA also decreased the expression of ki-67 and increased cleaved-caspase 3 expression in intestinal epithelia. Our data indicate that the GABAA Rs activation within colon mucosa disrupts the intestinal barrier and increases the intestinal permeability which facilitates inflammatory reaction in colon. Meanwhile, the suppression effect of GABA on pro-inflammatory cytokines leads to insufficient bacteria elimination and further aggravated the bacteria invasion and inflammatory damage.

【 授权许可】

Unknown