Research Article Mechanism underlying the reversal of contractility dysfunction in experimental colitis by cyclooxygenase-2 inhibition

Inflammatory bowel diseases are associated with reduced colonic contractility and induction of cyclooxyge- nase-2. In this study a possible role of cyclooxygenase-2 in and the underlying mechanism of the reduced contractil- ity were investigated in experimental colitis. The effects of meloxicam, a cyclooxygenase-2 selective inhibitor were examined on colonic contractility and MAP kinase p38 and ERK1/2 expression. Colitis was induced in Sprague-Dawley male rats by intra-colonic instillation of trinitrobenzenesul- phonic acid (TNBS; 40 mg/rat in 50% ethanol). The animals were divided into three groups. Group 1 (n=9) received mel- oxicam (3 mg/kg-day) gavage 1 h before and 1 day (Group 2) after induction of colitis. Group 3 (n=9) received phos- phate buffered saline (PBS) in a similar manner and served as colitic control. The non colitic control animals received meloxicam in a similar manner. The animals were sacrificed after 5 days of treatment, colon was cleaned with PBS and colonic smooth muscle was obtained which was used in this study. Meloxicam treatment given 1 h before or 1 day after administration of colitis restored the reduced colonic con- tractility without affecting the sensitivity to carbachol. The levels of colonic smooth muscle IL-1β mRNA, PGE2, ERK1/ 2, p38, malondialdehyde, myeloperoxidase activity and co- lonic mass were increased, whereas the body weight was decreased due to TNBS. The changes except colonic muscle mass and p38 expression were reversed by meloxicam treat- ment. These findings indicate that restoration of reduced colonic contractility by meloxicam is mediated by ERK1/2, and that ERK1/2 may serve as an important anti inflammatory target for treatment of colitis.