Nitric-oxide synthases glucocorticoids

Di Rosa, M., Radomski, M., Carnuccio, R. and Moncada, S. (1990). Glucocorticoids inhibit the induction of nitric oxide synthase in macrophages. Biochem. Biophys. Res. Commun. 173, 1246-1252. 

As in other tissues, glucocorticoids inhibit production of inflammatory cytokines (TNF-ct, IL-1) and chemokines (IL-8) reduce expression of inflammatory cell adhesion molecules and inhibit gene transcription of nitric oxide synthase, phospholipase A2, cydooxygenase-2, and NF- . 

In addition to direct effects on genes regulating inflammation, glucocorticoids also inhibit the transcription factors that initiate synthesis of pro-inflammatory cytokines (e.g., interleukin-1, tumor necrosis factor), enzymes (e.g., COX-2, nitric oxide synthase), and receptor proteins (e.g., natural killer receptors).17,87,89 Glucocorticoids may also exert some of their effects via a membrane-bound receptor that regulates activity of macrophages, eosinophils, T lymphocytes, and several other types of cells involved in the inflammatory response.89 Consequently, glucocorticoids affect many aspects of inflammation, and their powerful anti-inflammatory effects in rheumatoid arthritis result from their ability to blunt various cellular and chemical components of the inflammatory response. 

Radomdd MW, Palmer RMJ Moncada S. (1990b) Glucocorticoids iidiibit the e ession of an inducible but not the constitutive, nitric oxide synthase in vascular endothdial cdls Proc Natl Acad Sd USA 87 10043-10047. 

Saleh D, Ernst P, Lim S, Barnes PJ, Giad A. Increased formation of the potent oxidant peroxynitrite in the airways of asthmatic patients is associated with induction of nitric oxide synthase effect of inhaled glucocorticoid. FASEB J 12 (1998) 929-937. 

NITRERGIC STIMULANTS mimic, or cause the production and release of nitric oxide (NO), which is an important mediator that is synthesized on demand. The actions of nitric oxide are very widespread, and imbalance is likely to be involved in a number of disease states. Nitric oxide synthase (NOS) has a widespread distribution in the body, and isoforms are recognized specifically constitutive and inducible (iNOS) forms. Both forms are cytosolic, Ca /calmodulin and NADPH-dependent, and inhibited by L-arginine derivatives. Induction of iNOS is by various inflammatory cytokines, particularly those stimulated by bacterial lipopolysaccarides, including tumour necrosis factor a. interferon 7 and interleukin 1 p. Induction of iNOS only is inhibited by GLUCOCORTICOIDS. 

Knowles RG, Salter M, Brooks SL, Moncada S. Anti-inflammatory glucocorticoids inhibit the induction by endotoxin of nitric oxide synthase in the lung, liver and aorta of the rat. Biochem Biophys Res Commun 1990 172(3) 1042-1048. 

Szab6, C., Thiemermann, C., Wu, C. C., Perretti, M., and Vane, J. R. (1994a). Attenuation of the induction of nitric oxide synthase by endogenous glucocorticoids accounts for endotoxin tolerance in vivo. Proc. Natl. Acad. Set. U.S.A. 91, nX-TlS. 

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