Abstract
Inflammatory bowel disease (IBD), encompassing ulcerative colitis and Crohn’s disease, is a multifactorial inflammatory disease of the small intestine and colon. Many investigators have reported that l-glutamine (Gln) therapy improves outcomes of experimental colitis models, although the mechanism is not fully understood. Regarding the anti-inflammatory properties of Gln, we have shown that Gln can effectively deactivate cytosolic phospholipase A2 (cPLA2) by rapid induction of MAPK phosphatase (MKP)-1. In this study, we explore the possibility that Gln ameliorates dextran sulfate sodium (DSS)-induced colitis via MKP-1 induction, resulting in inhibition of cPLA2, which has been reported to play a key role in the pathogenesis of IBD. Oral Gln intake attenuated DSS-induced colitis. Gln inhibited cPLA2 phosphorylation, as well as colonic levels of TNF-α and leukotriene (LT)B4. Gln administration resulted in early and enhanced MKP-1 induction. Importantly, MKP-1 small interfering RNA (siRNA), but not control siRNA, significantly abrogated the Gln-mediated (1) induction of MKP-1; (2) attenuation of colitis (colon length, histological abnormality, and inflammation; and (3) inhibition of cPLA2 phosphorylation and colonic levels of TNF-α and LTB4. These data indicated that Gln ameliorated DSS-induced colitis via MKP-1 induction.
Highlights
Inflammatory bowel disease (IBD), encompassing ulcerative colitis and Crohn’s disease, is a multifactorial inflammatory disease of the small intestine and colon
We report that Gln ameliorated dextran sulfate sodium (DSS)-induced colitis via MAPK phosphatase (MKP)-1 induction, resulting in inhibition of cytosolic phospholipase A2 (cPLA2)
As for the mechanisms of Gln-mediated cPLA2 deactivation, we have reported that Gln deactivates cPLA2 either by dephosphorylating p38 [20,23], which is a major upstream that Gln deactivates cPLA2 either by dephosphorylating p38 [20,23], which is a major upstream pathway for cPLA2 phosphorylation [47], or by directly dephosphorylating cPLA2 due to enhanced pathway for cPLA2 phosphorylation [47], or by directly dephosphorylating cPLA2 due to enhanced physical interaction between Gln-induced MKP-1 and cPLA2 [24]
Summary
Inflammatory bowel disease (IBD), encompassing ulcerative colitis and Crohn’s disease, is a multifactorial inflammatory disease of the small intestine and colon. Factors implicated in the pathogenesis of IBD include heritable traits, environmental factors, abnormalities in intestinal mucosal barrier integrity and function [1,2], immune regulation [3,4], and gut microbiota [5]. Amino acids are key regulators of metabolic pathways, and evidence has indicated additional roles for amino acids in maintaining gut health [8]. Recent studies have indicated that L-glutamine (Gln) is important for intestinal metabolism, especially following stress [9], and Gln diets improve intestinal morphology and function [10,11,12]. Gln has long been studied as a promising agent to preserve intestinal function and recovery during injury or stress [13,14]. Many investigators have reported that Gln therapy improves outcomes of experimental colitis models. The mechanism by which Gln exerts its beneficial effects is not fully understood, it appears to be correlated with the improvement of Nutrients 2018, 10, 288; doi:10.3390/nu10030288 www.mdpi.com/journal/nutrients
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