TJN-419 Improves Dextran Sulfate Sodium-Induced Colitis via Inhibition of Interleukin-12 Release
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概要
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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.
- Pharmaceutical Society of Japanの論文
著者
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竹田 秀一
ツムラ研究本部
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Hattori Tomohisa
Tsumura & Co. Tsumura Res. Laboratories
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竹田 秀一
Tsumura & Co. Tsumura Res. Laboratories
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Takeda Shuichi
Department Of Drug Metabolism & Disposition Tsumura Research Institute Tsumura & Co.
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Sadakane Chiharu
Tsumura Research Laboratories Tsumura & Co.
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Hasegawa Yoshihiro
Tsumura Research Laboratories Tsumura & Co.
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Koseki Junichi
Tsumura Research Laboratories Tsumura & Co.
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Maruyama Hirobumi
Tsumura Research Laboratories Tsumura & Co.
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Takeda Hiroshi
Division Of Pharmasciences Department Of Pathophysiology And Therapeutics Faculty Of Pharmaceutical
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Shindo Shoichiro
Tsumura Research Laboratories Tsumura & Co.
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Takeda Shuichi
Tsumura & Co. Tsumura Research Laboratories
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