Interleukin-12 gene-expression of macrophages is regulated by nitric oxide.
Interleukin-12 is a heterodimeric cytokine, mainly produced by macrophages. In our present study we demonstrate that interleukin-12 expression is regulated by nitric oxide. Incubation of the macrophage cell line IC 21 with interferon-gamma gave rise to both interleukin-12 p40 mRNA and nitric oxide production. The concurrent addition of the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine inhibited nitrite production and in parallel completely suppressed interleukin-12 p40 mRNA formation. This indicated that endogenous nitric oxide synthase activity was required for IL-12 p40 gene expression. Exposure of the cells towards the nitric oxide generating compounds nitroprusside or S-nitroso-N-acetyl-penicillamine induced interleukin-12 p40 mRNA. Maximal mRNA levels were induced with nitric oxide donors at 1 microM concentration. We conclude that nitric oxide may exert an autoregulatory and paracrine control of interleukin-12 gene expression.
Rothe
H
H
Diabetes Research Institute, Heinrich- Heine University of Düsseldorf, Germany.
Hartmann
B
B
Geerlings
P
P
Kolb
H
H
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D007371:Interferon-gamma / Q000494:pharmacology; D018664:Interleukin-12 / Q000096:biosynthesis*; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011994:Recombinant Proteins; D026423:S-Nitroso-N-Acetylpenicillamine; D014158:Transcription, Genetic / Q000187:drug effects; D019323:omega-N-Methylarginine
D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D011994:Recombinant Proteins; D009599:Nitroprusside; D018664:Interleukin-12; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D007371:Interferon-gamma; D001120:Arginine; D019001:Nitric Oxide Synthase; D010396:Penicillamine