Dipeptidyl peptidase IV (DPPIV) degrades some peptide hormones and cytokines, resulting in homeostatic modulation. However, the role of DPPIV in inflammatory bowel diseases remains controversial. To determine the role of DPPIV in colitis, we used F344/DuCrlCrlj (F344/Du) rats as a DPPIV-deficient model. The serum DPPIV activity was much lower in the F344/Du rats than in F344/Jcl rats which were used as a DPPIV-positive model. Interestingly, the disease activity index (DAI) was different in the early phase of 2% dextran sulfate sodium (DSS)-induced colitis, as judged by the mucosal myeloperoxidase activity, colonic weight, and cecal fermentation. Similarly, retarded DAI was apparent in the DPPIV-deficient rats with 1% DSS-induced colitis. These findings suggest that a low level of DPPIV activity contributed to maintaining intestinal homeostasis by suppressing the cleavage of cytokines and growth hormones in DSS-induced colitis, especially in the early phase of colitis and with moderate inflammation.

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