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.
journal_name
Dig Dis Scijournal_title
Digestive diseases and sciencesauthors
Aggarwal S,Ahuja V,Paul Jdoi
10.1007/s10620-017-4662-3subject
Has Abstractpub_date
2017-10-01 00:00:00pages
2768-2779issue
10eissn
0163-2116issn
1573-2568pii
10.1007/s10620-017-4662-3journal_volume
62pub_type
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journal_title:Digestive diseases and sciences
pub_type: 杂志文章
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journal_title:Digestive diseases and sciences
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journal_title:Digestive diseases and sciences
pub_type: 杂志文章,meta分析,评审
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更新日期:2010-07-01 00:00:00
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journal_title:Digestive diseases and sciences
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更新日期:2008-05-01 00:00:00
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journal_title:Digestive diseases and sciences
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更新日期:1996-06-01 00:00:00
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journal_title:Digestive diseases and sciences
pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:Digestive diseases and sciences
pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:Digestive diseases and sciences
pub_type: 杂志文章
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更新日期:1998-11-01 00:00:00