Lack of bone marrow stromal cell antigen-1 (BST-1)/CD157 ameliorated colitis induced by dextran sodium sulfate (DSS)

Abstract

Abstract Bone marrow stromal cell antigen-1(BST-1)/CD157 is GPI-anchored ectoenzyme having adenosine diphosphate(ADP)-ribosyl cyclase and cyclic ADP-ribose hydrolase activities. BST-1 also functions as a receptor for signal transduction. Recently, various groups reported novel functions of BST-1, such as regulation of intestinal or mesenchymal stem cells. Re-analyses of BST-1 deficient mice (Bst1KO) in C57BL/6 background revealed roles in defense against tuberculosis, and prevention of depressive or anxious behaviors. Thus, BST-1 is now appreciated as an entero-neuro-immune regulator. Since expression of BST-1 in the intestines is common in human and mouse, we examined the roles for BST-1 in DSS-induced colitis using Bst1KO. Drinking water containing 3% DSS was supplied ad libitum to Bst1KO and C57BL/6 (WT) in SPF condition for 5 days, and then water without DSS for 2 days. Decreases of body weights in Bst1KO were similar to WT until day 5, but since then they became significantly slower than WT. Clinical scores based on bleeding and diarrhea were similar in both genotypes. Histological analyses with HE staining revealed the ratio of destroyed epitheliums in the total colon of Bst1KO was 15% whereas that of WT was 50%. Flow cytometrical analyses revealed no difference in the cell numbers of neutrophils and macrophages increased in the colon at day 7. Quantitative real-time PCR revealed that increases of Bst1 expression in the colons of WT started on day 1 and reached to the level more than thousand times at day 5. In the colons of Bst1KO, increases of Il6 expression at day 5 were markedly decreased compared with those of WT. These data indicate that BST-1 has pro-inflammatory roles in DSS-induced colitis through positive regulation of IL-6 production.