Effects Of P38MAPK Inhibitor SB203580 On DSS-induced Colitis Model In Mice

Background and AimsUlcerative colitis(UC) is non-specific inflammatory disorder involving in primarily the mucosa and submucosa of colon. Although the exact phathogenesis of UC is still unknown, it has been widely accepted that dysregulated mucosal immune response was involved in development of the disorder. Cytokines have been shown to play a critical role in the phathogenesis of UC. P38 Mitogen-activated protein kinase(P38MAPK) has been demonstrated to correlate with produce and modulation of various cytokines. Thus ,the aims of the study were to investigate the effects of SB203580,a special P38MAPK inhibitor,on dextran sulphate sodium(DSS)-induced colitis model in mice in order to provide experimental evidence that SB203580 serves as a possible novel drug for treatment of UC.MethodsDSS-induced colitis mice and control mice were divided into three group:normal control, DSS-induced colitis, DSS-induced colitis plus SB203580 1mg/kg body weight i.p once daily beginning 72h after DSStreatment and continuing until death as indicated. The mice were sacrificed after 7 days. Colitis was evaluated by the disease activity index(DAI) and histological score. TNF-a levels were measured by Enzyme-linked immunoadsordent assay(ELISA). P-ATF2 expression in intestinal inflammatory cells were determined by Immunohistochemistry(IHC) staining.Results1. DAI significantly increased in DSS-induced colitis compared with normal control group (PO.05) . But SB203580 reduced markedly the disease activity (DAI) of DSS-induced colitis (PO.05 ) .2. Histological score significantly increased in DSS-induced colitis compared with normal control group (P<0.05) . But SB203580 reduced markedly the histological score of DSS-induced colitis (PO.05) .3. TNF-a level significantly increasd in DSS-induced colitis compared with normal control group (PO.05). But SB203580 down-regulated markedly TNF-a in DSS-induced colitis (PO.05) .4. The expression of P-ATF2 in intestinal inflammatory cells in DSS-induced colitis significantly increased compared with normal control group (PO.05 ) . But SB203580 reduced markedly the expression ofP-ATF2 in DSS-induced colitis (PO.05) .ConclusionsInhibition of P38MAPK signal transduction pathway by SB203580 could improve the clinical score, ameliorate the histological alteration, .reduce the TNF-a levels and P-ATF2 expression. This results suggest that P38MAPK signal transduction pathway could play a pivotal role in the pathogenesis of DSS-induced colitis model. This model was very similar to human UC.Therefore, P38MAPK could represent a novel target for future therapies inhuman UC.