| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Research Abstract |
Tumor necrosis factor-α (TNF-α) has a pivotal role in the pathogenesis of rheumatoid arthritis (RA). TNF-α is produced largely by monocyte-like synoviocytes (MLS) in the inflammatory synovium in RA, and is an important therapeutic target in RA. Butyrare is a natural product of intestinal bacterial flora and has anti-inflammatory effects of the luminal environment by inhibiting the production of TNF-α, the precise mechanism is yet unclear. In this study, butyrate suppressed TNF-α secretion by primary synoviocytes, as well as peripheral monocytes and murine RAW264.7 macrophage cells. In these cells, butyrate suppressed TNF-α mRNA expression, but did not inhibit the transnational activity driven through the TNF-α promoter. In addition, the inhibitory effect of butyrate on TNF-α mRNA expression was dependent on the AU-rich element (ARE) in 3' untranslated region (UTR) of the TNF-α transcripts, which was known to be involved in the regulation of TNF-α mRNA turnover. As a candidate molecule that mediate butyrate-dependent TNF-α mRNA inhibition, TIS11B was indicated that as the mRNA was induced in monocytes by butyrate. When TIS11B was overexpressed in monocytes, TNF-α gene induction by LPS was significantly inhibited. It was concluded that TIS11B is a candidate factor that mediates inhibitory action of butyrate on TNF-α expression.
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