Main content area

<span style="font-variant: small-caps;">l</span>-Glutamine Attenuates DSS-Induced Colitis via Induction of MAPK Phosphatase-1

Jeong, Soo-Yeon, Im, Yoo Na, Youm, Ji Young, Lee, Hern-Ku, Im, Suhn-Young
Nutrients 2018 v.10 no.3
Crohn disease, anti-inflammatory activity, colitis, colon, dextran sulfate, glutamine, histology, inflammation, mitogen-activated protein kinase, models, pathogenesis, phospholipases, phosphorylation, small interfering RNA, small intestine, therapeutics, tumor necrosis factor-alpha
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 A<inf>2</inf> (cPLA<inf>2</inf>) 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 cPLA<inf>2</inf>, which has been reported to play a key role in the pathogenesis of IBD. Oral Gln intake attenuated DSS-induced colitis. Gln inhibited cPLA<inf>2</inf> phosphorylation, as well as colonic levels of TNF-α and leukotriene (LT)B<inf>4</inf>. 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 cPLA<inf>2</inf> phosphorylation and colonic levels of TNF-α and LTB<inf>4</inf>. These data indicated that Gln ameliorated DSS-induced colitis via MKP-1 induction.