Keith Wilson
Faculty Member
Last active: 11/2/2019

L-arginine supplementation improves responses to injury and inflammation in dextran sulfate sodium colitis.

Coburn LA, Gong X, Singh K, Asim M, Scull BP, Allaman MM, Williams CS, Rosen MJ, Washington MK, Barry DP, Piazuelo MB, Casero RA, Chaturvedi R, Zhao Z, Wilson KT
PLoS One. 2012 7 (3): e33546

PMID: 22428068 · PMCID: PMC3299802 · DOI:10.1371/journal.pone.0033546

Inflammatory bowel disease (IBD), consisting of Crohn's disease and ulcerative colitis (UC), results in substantial morbidity and is difficult to treat. New strategies for adjunct therapies are needed. One candidate is the semi-essential amino acid, L-arginine (L-Arg), a complementary medicine purported to be an enhancer of immunity and vitality in the lay media. Using dextran sulfate sodium (DSS) as a murine colonic injury and repair model with similarities to human UC, we assessed the effect of L-Arg, as DSS induced increases in colonic expression of the y(+) cationic amino acid transporter 2 (CAT2) and L-Arg uptake. L-Arg supplementation improved the clinical parameters of survival, body weight loss, and colon weight, and reduced colonic permeability and the number of myeloperoxidase-positive neutrophils in DSS colitis. Luminex-based multi-analyte profiling demonstrated that there was a marked reduction in proinflammatory cytokine and chemokine expression with L-Arg treatment. Genomic analysis by microarray demonstrated that DSS-treated mice supplemented with L-Arg clustered more closely with mice not exposed to DSS than to those receiving DSS alone, and revealed that multiple genes that were upregulated or downregulated with DSS alone exhibited normalization of expression with L-Arg supplementation. Additionally, L-Arg treatment of mice with DSS colitis resulted in increased ex vivo migration of colonic epithelial cells, suggestive of increased capacity for wound repair. Because CAT2 induction was sustained during L-Arg treatment and inducible nitric oxide (NO) synthase (iNOS) requires uptake of L-Arg for generation of NO, we tested the effect of L-Arg in iNOS(-/-) mice and found that its benefits in DSS colitis were eliminated. These preclinical studies indicate that L-Arg supplementation could be a potential therapy for IBD, and that one mechanism of action may be functional enhancement of iNOS activity.

MeSH Terms (24)

Amino Acids Animals Arginine Blotting, Western Cationic Amino Acid Transporter 2 Cell Movement Chemokines Colitis, Ulcerative Cytokines Dextran Sulfate Dietary Supplements DNA Primers Epithelial Cells Gene Expression Regulation Immunohistochemistry Mice Mice, Inbred C57BL Mice, Knockout Microarray Analysis Neutrophils Nitric Oxide Synthase Type II Organ Size Permeability Weight Loss

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