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- Title
Attenuated GABAergic Signaling in Intestinal Epithelium Contributes to Pathogenesis of Ulcerative Colitis.
- Authors
Aggarwal, Surbhi; Ahuja, Vineet; Paul, Jaishree
- Abstract
<bold>Background: </bold>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.<bold>Aims: </bold>This study was carried out to investigate the role of GABA and its signaling components in pathogenesis of UC.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Subjects
ULCERATIVE colitis; GABAERGIC neurons; IMMUNE response; AMINOBUTYRIC acid; ENZYME-linked immunosorbent assay; MITOGEN-activated protein kinases; CYTOKINES; MICROBIOLOGY; COLON microbiology; BACTERIA; BIOCHEMISTRY; BIOPSY; CELL receptors; CELLULAR signal transduction; COLON (Anatomy); FECES; GABA; INFLAMMATORY mediators; INTESTINAL mucosa; PHENOMENOLOGY; TRANSFERASES; CASE-control method
- Publication
Digestive Diseases & Sciences, 2017, Vol 62, Issue 10, p2768
- ISSN
0163-2116
- Publication type
journal article
- DOI
10.1007/s10620-017-4662-3