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 f rom multifocal inflammation and die by 3-4 wk of age. In these mice, l evels of nitric oxide (NO) reaction products in serum are elevated app roximately fourfold over levels in controls, peaking at 15-17 d of lif e. Shortterm treatment of TGF-beta 1(-/-) mice with N-G-monomethyl-L-a rginine suppressed this elevated production of NO. Expression of induc ible NO synthase (iNOS) mRNA and protein is increased in the kidney an d heart of TGF-beta 1(-/-) mice. These findings demonstrate that TGF-b eta 1 negatively regulates iNOS expression in vivo, as had been inferr ed from mechanistic studies on the control of iNOS expression by TGF-b eta 1 in vitro.