Surbhi Aggarwal1, Vineet Ahuja2, Jaishree Paul3. 1. School of Life Sciences, Jawaharlal Nehru University, New Delhi, 110067, India. 2. Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, 110067, India. 3. School of Life Sciences, Jawaharlal Nehru University, New Delhi, 110067, India. jpaul33@hotmail.com.
Abstract
BACKGROUND: Neuromediators produced by enteric nervous system regulate inflammatory processes via interacting with enteric immune system. Role of γ-aminobutyric acid (GABA), which is also a neuromediator, has been implicated in autoimmune diseases like multiple sclerosis, type 1 diabetes, and rheumatoid arthritis, where they modulate the immune responses. However, its role in ulcerative colitis (UC) has not been defined. AIMS: This study was carried out to investigate the role of GABA and its signaling components in pathogenesis of UC. METHODS: Peripheral blood, colon mucosal biopsy, and fecal specimens were collected from UC and control groups. Quantification of GABA was done using ELISA. Expression of GABAergic signal system components was analyzed through RT-PCR analysis. Enumeration of GABA-producing bacteria was done by qPCR analysis. Activity of p38 MAPK and expression of proinflammatory cytokines were determined by immunohistochemistry and RT-PCR analysis, respectively. RESULTS: GABA levels were significantly reduced in patients with UC as compared to control group when measured in serum and colon biopsy. Altered expression of GABAergic signal system was observed in UC patients. Reduced abundance of selected GABA-producing bacteria was detected in stool samples of UC patients as compared to control. p38 MAPK activity and expression of its downstream effector cytokines were found to be increased in UC patients as compared to control. CONCLUSIONS: Reduced levels of GABA were observed in patients with UC, and this leads to hyperactivation of p38 MAPK and overexpression of downstream effector cytokines suggesting a role of GABA in pathogenesis of UC.
BACKGROUND: Neuromediators produced by enteric nervous system regulate inflammatory processes via interacting with enteric immune system. Role of γ-aminobutyric acid (GABA), which is also a neuromediator, has been implicated in autoimmune diseases like multiple sclerosis, type 1 diabetes, and rheumatoid arthritis, where they modulate the immune responses. However, its role in ulcerative colitis (UC) has not been defined. AIMS: This study was carried out to investigate the role of GABA and its signaling components in pathogenesis of UC. METHODS: Peripheral blood, colon mucosal biopsy, and fecal specimens were collected from UC and control groups. Quantification of GABA was done using ELISA. Expression of GABAergic signal system components was analyzed through RT-PCR analysis. Enumeration of GABA-producing bacteria was done by qPCR analysis. Activity of p38 MAPK and expression of proinflammatory cytokines were determined by immunohistochemistry and RT-PCR analysis, respectively. RESULTS:GABA levels were significantly reduced in patients with UC as compared to control group when measured in serum and colon biopsy. Altered expression of GABAergic signal system was observed in UC patients. Reduced abundance of selected GABA-producing bacteria was detected in stool samples of UC patients as compared to control. p38 MAPK activity and expression of its downstream effector cytokines were found to be increased in UC patients as compared to control. CONCLUSIONS: Reduced levels of GABA were observed in patients with UC, and this leads to hyperactivation of p38 MAPK and overexpression of downstream effector cytokines suggesting a role of GABA in pathogenesis of UC.
Authors: Judith Aron-Wisnewsky; Edi Prifti; Eugeni Belda; Farid Ichou; Brandon D Kayser; Maria Carlota Dao; Eric O Verger; Lyamine Hedjazi; Jean-Luc Bouillot; Jean-Marc Chevallier; Nicolas Pons; Emmanuelle Le Chatelier; Florence Levenez; Stanislav Dusko Ehrlich; Joel Dore; Jean-Daniel Zucker; Karine Clément Journal: Gut Date: 2018-06-13 Impact factor: 23.059
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