Nitric Oxide and Nitric Oxide Synthase mRNA Induction in Mouse Islet Cells by Interferon-γ Plus Tumor Necrosis Factor-α

• Published in: Biochemical and biophysical research communications Vol. 197; no. 1; pp. 22 - 27
• Main Authors: Yamada, K., Otabe, S., Inada, C., Takane, N., Nonaka, K.
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 30.11.1993; Elsevier
• Subjects: Amino Acid Oxidoreductases - biosynthesis; Amino Acid Oxidoreductases - genetics; Analytical, structural and metabolic biochemistry; Animals; Arginine - analogs & derivatives; Arginine - pharmacology; Base Sequence; Biological and medical sciences; Cells, Cultured; Cycloheximide - pharmacology; Cytokines - pharmacology; Enzyme Induction - drug effects; Fundamental and applied biological sciences. Psychology; Interferon-gamma - pharmacology; Islets of Langerhans - enzymology; Islets of Langerhans - metabolism; Mice; Molecular Sequence Data; Nitric Oxide - antagonists & inhibitors; Nitric Oxide - biosynthesis; Nitric Oxide Synthase; omega-N-Methylarginine; Protein hormones. Growth factors. Cytokines; Proteins; RNA, Messenger - biosynthesis; Tumor Necrosis Factor-alpha - pharmacology; Enzyme; Cytokine; Rodentia; Langerhans islet; Cytotoxicity; Biosynthesis; Gene expression; Nitric-oxide synthase; Vertebrata; Mammalia; Mouse; Nitrogen monoxide; Oxidoreductases; Mechanism of action; Tumor necrosis factor α; Gamma interferon
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1993.2435

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-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) 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-γ and TNF-α, 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-γ plus TNF-α.