抄録
Dipeptidyl peptidase IV (DP IV, CD26) is a serine exopeptidase which selectively cleaves the penultimate proline residue of polypeptides. This enzyme is also expressed on activated T cells. To assess the relevance of DP IV in immunological disorders, we evaluated the pharmacological effects of specific DP IV inhibitors. A competitive inhibitor of DP IV, Lys (Z (NO2) ) -thiazolidide suppressed mitogen-induced and antigen-induced proliferation of T cells. In vivo pharmacological effects were assessed by using alkyldiamine-and collagen-induced arthritis models, which share several pathological features with rheumatoid arthritis. A competitive inhibitor of DP IV (Lys (Z (NO2) ) -thiazolidide), an irreversible inhibitor (Ala-Pro-nitrobenzoyl hydroxylamime), and a transition state substrate analog of DP IV (Ala-boroPro) suppressed alkyldiamine-induced arthritis. Ala-boroPro also suppressed collagen-induced arthritis. These results suggest that DP IV may play a role in the pathogenesis of certain inflammatory diseases through immune regulation.
