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TJN-419 Improves Dextran Sulfate Sodium-Induced Colitis via Inhibition of Interleukin-12 Release
| Title: | TJN-419 Improves Dextran Sulfate Sodium-Induced Colitis via Inhibition of Interleukin-12 Release |
| Authors: | Sadakane, Chiharu Browse this author | | Koseki, Junichi Browse this author | | Inagaki, Yayoi Browse this author | | Hasegawa, Yoshihiro Browse this author | | Shindo, Shoichiro Browse this author | | Maruyama, Hirofumi Browse this author | | Takeda, Shuichi Browse this author | | Takeda, Hiroshi Browse this author | | Hattori, Tomohisa Browse this author |
| Keywords: | TJN-419 | | dextran sulfate sodium-induced colitis | | interleukin-12 | | clinical index |
| Issue Date: | 2010 |
| Publisher: | Pharmaceutical Society of Japan |
| Journal Title: | Biological & Pharmaceutical Bulletin |
| Volume: | 33 |
| Issue: | 1 |
| Start Page: | 84 |
| End Page: | 90 |
| Publisher DOI: | 10.1248/bpb.33.84 |
| Abstract: | We investigated the association of interleukin-12 (IL-12) with development of dextran sulfate sodium (DSS)-induced colitis in mice, and examined the effects of TJN-419, a synthetic compound derived from acteoside, on this process. Enhanced IL-12 production in lipopolysaccharide (LPS)-stimulated macrophages was dose-dependently inhibited by addition of TJN-419 to culture medium, and this effect was abolished by pretreatment with PD98059, an inhibitor of extracellular-regulated kinase. We then assessed the effect of TJN-419 or a neutralizing antibody against murine IL-12 in a DSS-induced colitis model in C57 BL/6 mice. Colitis was induced by 5% DSS solution given as drinking water. Treatment with the anti-IL-12 antibody was performed intravenously and TJN-419 was administered orally. We also investigated the effect of TJN-419 on erosion in the rectum in a DSS-induced colitis model in rat. The IL-12 level in the rectum was significantly enhanced and the IL-10 level was significantly decreased in animals with DSS-induced colitis compared with untreated controls. Intravenous injection of the anti-IL-12 antibody and oral administration of TJN-419 inhibited clinical symptoms in DSS-induced colitis. TJN-419 also inhibited the increase in IL-12 and suppressed the area of erosion in the rectum in DSS-induced colitis in rats. These results indicate that IL-12 has a possible role in development of DSS-induced colitis and that TJN-419 is effective for treatment of this disease model via inhibition of IL-12 production. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/42526 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 武田 宏司
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