Regulation of inducible nitric oxide synthase mRNA levels by LPS, INF-gamma, TGF-beta, and IL-10 in murine macrophage cell lines and rat peritoneal macrophages.
The molecular mechanisms of LPS, INF-gamma, TGF-beta, and IL-10 regulation of inducible nitric oxide synthase (iNOS) mRNA expression were evaluated. In murine macrophage cell lines, LPS-induced increases in iNOS mRNA were blocked by either cycloheximide or actinomycin D. Neither TGF-beta nor IL-10 alone had any effect on basal expression, and each only slightly reduced LPS induction of iNOS mRNA. However, IL-10 augmented INF-gamma induction of iNOS mRNA to very high levels, while TGF-beta inhibited INF-gamma induction. Human monocytes expressed no detectable iNOS mRNA with any stimuli, though Southern analysis on human genomic DNA revealed a specific human iNOS gene. In human macrophages, the iNOS gene may have become inoperative during evolution.
Chesrown
S E
SE
Department of Pediatrics, University of Florida, Gainesville 32610.
Monnier
J
J
Visner
G
G
Nick
H S
HS
D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D015139:Blotting, Southern; D002460:Cell Line; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004790:Enzyme Induction; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D016753:Interleukin-10 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology; D019001:Nitric Oxide Synthase; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D003609:Dactinomycin; D007371:Interferon-gamma; D003513:Cycloheximide; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases