Effects of alanyl-glutamine dipeptide on the expression of colon-inflammatory mediators during the recovery phase of colitis induced by dextran sulfate sodium.

PURPOSE: Glutamine (Gln) is a nutrient with immunomodulatory effects in metabolic stressed conditions. This study investigated the effects of Gln on colonic-inflammatory-mediator expression and mucosal repair in mice with dextran sulfate sodium (DSS)-induced colitis.

METHODS

C57BL/6 mice received distilled water containing 3 % DSS for 5 d to induce colitis. One of the DSS-treated groups was intraperitoneally injected with an alanyl (Ala)-Gln solution 3 days before (G-DSS) while the other group was administered Ala-Gln 3 days after colitis (DSS-G) was induced. The Ala-Gln solution provided 0.5 g Gln/kg/d. The saline-DSS group (S-DSS) received an identical amount of saline before and after colitis was induced to serve as a positive control.

RESULTS

The S-DSS group had a shorter colon length, higher plasma haptoglobin level, and more-severe colon inflammation. Also, the toll-like receptor (TLR)4 level, nuclear factor (NF)-κB activation, and inflammatory cytokine gene expression in the colon were higher than those of the normal control group. Gln administration either before or after colitis suppressed TLR4 protein levels, decreased plasma haptoglobin, and reduced colon inflammation. Histological inflammatory scores were also lowered. Compared to the post-colitis Gln group, preventive use of Gln had higher colon length, expressions of mucin 2, trefoil factor 3, and heat shock protein 72 genes were also upregulated in the colon.

CONCLUSIONS

These results suggest that Gln administered either before or after the colitis mitigated inflammation of colitis that was not observed in group without Gln injection. Prophylactic treatment with Gln had more-beneficial effects on reducing inflammatory markers and enhancing the recovery of mucosa in DSS-induced colitis.