Control of nitric oxide production by transforming growth factor-beta1: mechanistic insights and potential relevance to human disease.
Studies on the multifunctional nature of the transforming growth factor-beta (TGF-beta) family of cytokines and the enzyme nitric oxide synthase (NOS) have suggested that they mediate a wide variety of vital processes in evolutionarily divergent organisms. Numerous mechanistic studies have investigated the consequences of the regulation of NO by the TGF-beta's for mammalian physiology. Studies with several cell types in vitro indicate that TGF-beta1 negatively controls the expression of the enzyme responsible for the prolonged production of large amounts NO, the inducible nitric oxide synthase (NOS2; iNOS), by reducing the expression and activity of NOS2 at multiple levels. Recent studies with TGF-beta1 null mice or mice which overexpress TGF-beta1 suggest that this cytokine may be a primary negative regulator of NOS2 in vivo. The interaction between NOS2 and TGF-beta1 may represent a central homeostatic mechanism in mammalian physiology with implications for a variety of human diseases.
Vodovotz
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Radiation Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D016212:Transforming Growth Factor beta; D009569:Nitric Oxide