Effects of Dipeptide Arginine‐Glutamine (Arg‐Gln) on Proliferation, Inflammation and Barrier Function in Intestinal Epithelial Cells

Glutamine (Gln) and arginine play important roles in intestinal functions. However, the effects of the stable dipeptide Arginyl‐glutamine (Arg‐Gln) on intestinal epithelial cells have not been investigated. We hypothesized that Arg‐Gln will provide benefits of both amino acids. Caco‐2 cells were treated with various doses of Arg‐Gln in Gln‐free medium for 72 h; MTS assay was performed to evaluate cell proliferation. In a separate experiment, cells were pretreated with Arg‐Gln in Gln‐free medium for 24 h in the presence or absence of endogenous Gln inhibitor methionine sulfoximine (MS), and then treated with LPS for another 48 h. Monolayer integrity was assayed by measuring transepithelial electrical resistance (TER). IL‐8 production in culture medium was determined by ELISA. Arg‐Gln supplementation increased cell proliferation in a dose dependent manner by 2.4 fold at 4mM (p<0.05). Under Gln deprivation condition, LPS induced IL‐8 production by 13 fold compared to control (p<0.01). Arg‐Gln pretreatment reversed this effect with a decreased IL‐8 by 40% (p<0.05) compared to LPS. Glutamine deprivation and LPS stimulation decreased TER by 45% (p<0.05). Arg‐Gln increased TER by 64% compared to LPS treated cells. Thus, the dipeptide Arg‐Gln supplementation has beneficial effects on cell proliferation, anti‐inflammation and epithelial integrity in Caco‐2 cells.