Nitric oxide and nitric oxide synthase mRNA induction in mouse islet cells by interferon-gamma plus tumor necrosis factor-alpha.
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.
Yamada
K
K
Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan.
Otabe
S
S
Inada
C
C
Takane
N
N
Nonaka
K
K
D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001483:Base Sequence; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects*; D007371:Interferon-gamma / Q000494:pharmacology; D007515:Islets of Langerhans / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase; D012333:RNA, Messenger / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019323:omega-N-Methylarginine
D016207:Cytokines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D007371:Interferon-gamma; D001120:Arginine; D003513:Cycloheximide; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases