Spontaneously increased production of nitric oxide and aberrant expression of the inducible nitric oxide synthase in vivo in the transforming growth factor beta 1 null mouse.
Transforming growth factor beta 1 null mice (TGF-beta 1-/-) suffer from multifocal inflammation and die by 3-4 wk of age. In these mice, levels of nitric oxide (NO) reaction products in serum are elevated approximately fourfold over levels in controls, peaking at 15-17 d of life. Shortterm treatment of TGF-beta 1-/- mice with NG-monomethyl-L-arginine suppressed this elevated production of NO. Expression of inducible NO synthase (iNOS) mRNA and protein is increased in the kidney and heart of TGF-beta 1-/- mice. These findings demonstrate that TGF-beta 1 negatively regulates iNOS expression in vivo, as had been inferred from mechanistic studies on the control of iNOS expression by TGF-beta 1 in vitro.
Vodovotz
Y
Y
Laboratory of Chemoprevention, National Institutes of Health, Bethesda, Maryland 20892, USA.
Geiser
A G
AG
Chesler
L
L
Letterio
J J
JJ
Campbell
A
A
Lucia
M S
MS
Sporn
M B
MB
Roberts
A B
AB
D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015152:Blotting, Northern; D004790:Enzyme Induction; D015870:Gene Expression / Q000187:drug effects*; D005838:Genotype; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000032:analysis / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D007668:Kidney / Q000201:enzymology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009206:Myocardium / Q000201:enzymology; D019331:NG-Nitroarginine Methyl Ester; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D009573:Nitrites / Q000097:blood; D010446:Peptide Fragments / Q000276:immunology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D012016:Reference Values; D016212:Transforming Growth Factor beta / Q000172:deficiency* / Q000235:genetics; D019323:omega-N-Methylarginine
D007527:Isoenzymes; D009566:Nitrates; D009573:Nitrites; D010446:Peptide Fragments; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester