2024-03-29T11:56:21Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/425262022-11-17T02:08:08Zhdl_2115_20044hdl_2115_124TJN-419 Improves Dextran Sulfate Sodium-Induced Colitis via Inhibition of Interleukin-12 ReleaseSadakane, ChiharuKoseki, JunichiInagaki, YayoiHasegawa, YoshihiroShindo, ShoichiroMaruyama, HirofumiTakeda, ShuichiTakeda, HiroshiHattori, TomohisaTJN-419dextran sulfate sodium-induced colitisinterleukin-12clinical index499We 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 JapanJournal Articleapplication/pdfhttp://hdl.handle.net/2115/42526https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/42526/1/BPB33-1_84-90.pdfBiological & Pharmaceutical Bulletin33184902010enginfo:doi/10.1248/bpb.33.84publisher