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Nitric oxide and nitric oxide synthase mRNA induction in mouse islet cells by interferon-gamma plus tumor necrosis

K Yamada1, S Otabe, C Inada

  • 1Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan.

It has been shown that nitric oxide (NO) is involved in islet cell damage induced by interleukin-1 (IL-1). Here we show that interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) synergistically induced NO production and inducible NO synthase (iNOS) mRNA expression in mouse islet cells. Cycloheximide (CXH) did not prevent the iNOS mRNA expressions. The combination of IFN-gamma and TNF-alpha, which is highly cytotoxic to mouse islet cells, failed to destruct islet cells in the absence of L-arginine or in the presence of NG-monomethyl-L-arginine (NMMA). These observations suggest that NO is a primary effector in islet cell damage caused by IFN-gamma plus TNF-alpha.

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