Protective role of uncoupling protein-2 against dextran sodium sulfate-induced colitis.

BACKGROUND AND AIMS: Uncoupling protein-2 (UCP-2) is a negative regulator of reactive oxygen species (ROS) production. We investigated the effect of UCP-2 on disease progression in a murine dextran sodium sulfate (DSS)-induced colitis model, and the expression and distribution of tight junction (TJ) proteins, such as occludin, zonula-1 (ZO-1), claudin-4, and junctional adhesion molecule-1 (JAM-1).

METHODS: Male UCP-2(-/-) mice and wild-type littermates were divided into four groups: groups I and II, which comprised each type of mouse, were administered 2.5% DSS dissolved in drinking water to create a colitis model. The control groups (groups III and IV, which comprised each type of mouse) were given normal drinking water. Disease progression was evaluated according to colon length and the disease activity index. The distribution of TJ proteins was detected by immunohistochemical analysis.

RESULTS: Compared with wild-type littermates, UCP-2(-/-) mice treated with DSS developed more severe diarrhea, body weight loss (P < 0.01), significantly short colon length, and more inflammatory cell infiltration into the mucosa and submucosa. The level of malondialdehyde in colonic mucosa increased in UCP-2(-/-) mice treated with DSS compared with the wild-type littermates (P < 0.001). The distribution of the ZO-1 and JAM-1 proteins was significantly decreased in the colonic mucosa of UCP-2(-/-) mice compared with the wild-type littermates, whereas occludin and claudin-4 distribution were not different between the UCP-2(-/-) mice and wild-type littermates.

CONCLUSIONS: UCP-2 might reduce intestinal inflammatory response through the negative regulation of ROS, and affects the expression and distribution of TJ proteins.