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TJN-419 Improves Dextran Sulfate Sodium-Induced Colitis via Inhibition of Interleukin-12 Release

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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
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
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 武田 宏司

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