Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Oxidoreductases / biosynthesis*
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Amino Acid Oxidoreductases / genetics
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Animals
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Arginine / analogs & derivatives
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Arginine / pharmacology
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Base Sequence
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Cells, Cultured
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Cycloheximide / pharmacology
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Cytokines / pharmacology*
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Enzyme Induction / drug effects*
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Interferon-gamma / pharmacology
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Islets of Langerhans / enzymology
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Islets of Langerhans / metabolism*
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Mice
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Molecular Sequence Data
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Nitric Oxide / antagonists & inhibitors
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Nitric Oxide / biosynthesis*
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Nitric Oxide Synthase
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RNA, Messenger / biosynthesis
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Tumor Necrosis Factor-alpha / pharmacology
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omega-N-Methylarginine
Substances
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Cytokines
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RNA, Messenger
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Tumor Necrosis Factor-alpha
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omega-N-Methylarginine
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Nitric Oxide
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Interferon-gamma
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Arginine
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Cycloheximide
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Nitric Oxide Synthase
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Amino Acid Oxidoreductases