l-Glutamine Attenuates DSS-Induced Colitis via Induction of MAPK Phosphatase-1

Nutrients. 2018 Mar 1;10(3):288. doi: 10.3390/nu10030288.

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.

Keywords: DSS; MKP-1; cPLA2; glutamine; inflammatory bowel disease.

MeSH terms

  • Animals
  • Colitis / chemically induced*
  • Colitis / drug therapy
  • Dextran Sulfate / toxicity*
  • Dual Specificity Phosphatase 1 / genetics
  • Dual Specificity Phosphatase 1 / metabolism*
  • Enzyme Induction / drug effects*
  • Glutamine / therapeutic use*
  • Mice
  • Specific Pathogen-Free Organisms

Substances

  • Glutamine
  • Dextran Sulfate
  • Dual Specificity Phosphatase 1