Paricalcitol Ameliorated Dextran-Sulfate-Sodium-Induced Colitis in Mice through MKP-1/P38 MAPK Signaling Pathway

Abstract

Background and Aim: Ulcerative Colitis (UC), a type of inflammatory bowel disease, of which the accurate pathogenesis is not yet well understand. Recently, the Vitamin D/VDR signaling pathway and the activated vitamin D analogues have been proved as playing important role in the pathogenesis of UC. In the present study, our objective was to evaluate the effect of Vitamin D analogues paricalcitol on dextran-sulfate-sodium-induced colitis in a mouse model. Methods: We evaluated the effects of the activated vitamin D analogues paricalcitol on the development of Dextran-Sulfate-Sodium-(DSS)-induced colitis. Clinical symptoms were evaluated by the Disease Activity Index (DAI) and tissue samples were evaluated by Histopathological Scoring (HS). Meanwhile, the mucosal mRNA expression of cytokines, Tumor Necrosis Factoralpha (TNF-a), Interleukin-6 (IL-6), Interleukin-10 (IL-10), Interleukin-17 (IL-17) were analyzed by real-time semi quantitative reverse transcription polymerase chain reaction. The mucosal protein VDR, p38 Mitogen-Activated Protein Kinase (P38-MAPK) and Mitogen-Activated Protein Kinase Phosphatase-1 (MKP-1) expressions of the vitamin D/VDR signaling pathway were analyzed using Western blot. Results: The results showed that the weight loss and colon length shortening of DSS-induced mice were significantly improved after paricalcitol treatment. In addition, both DAI and HS were significantly reduced. Paricalcitol down regulated the mucosal expression of messenger RNA of pro-inflammatory cytokines TNF-a, IL-6 and IL-10 and upregulated anti-inflammatory cytokines IL-17. Both VDR protein expression and MKP-1 level increased, whereas the mucosal expression of p38-MAPK was found to be decreased. Conclusion: Activated Vitamin D analogues paricalcitol can ameliorate the development of DSS-induced colitis through the Vitamin D/VDR signaling pathway.