Nitric oxide transcription regulation

Lin, Y.L. and Lin, J.K., (-)-Epigallocatechin-3-gallate blocks the induction of nitric oxide synthase by down-regulating lipopolysaccharide-induced activity of transcription factor nuclear factor-kappaB, Mol Pharmacol, 52, 465, 1997. 

Micromolar quantities of RNS are generated primarily by nitric oxide synthase 2 (NOS2), an enzyme that is up-regulated during colon-cancer progression. As discussed below, deoxycholate (DOC), a hydrophobic secondary bile acid, activates the redox-sensitive transcription factor NF-kB, resulting in increased levels of NOS2 and enhanced S-nitrosylation of proteins. Additional sources of bile-acid-induced ROS and RNS are also likely. ... 

In addition we have shown that IL-1 also induces the expression of c-jun in both islets and RINm5F cells, and have obtained preliminary evidence for nuclear factor RB (NF-kB) activation (J. A. Corbett and M. L. McDaniel, unpublished observation). TTiese three transcriptional regulators alone or in combination are believed to participate in IL-1-induced expression of nitric oxide synthase by the islet j8 cell. Importantly, Nathan and co-workers have shown the presence of NF-kB response elements upstream of the mouse macrophage iNOS gene (Xie et cd., 1993). 

We have proposed a mechanism by which lL-1 exerts its deleterious effects on islet function and viability (Fig. 11 Corbett et al., 1992). In this proposed mechanism, lL-1 is released by macrophages during the initial stages of islet infiltration. IL-1 binds to a specific IL-1 receptors on the /3 cell activating a tyrosine kinase. Tyrosine kinase phosphorylation stimulates second messengers to induce the expression of c-/os, c-jun, the activation of NF-xB, and possibly other early transcriptional regulators. These early-immediate transcriptional response elements may activate or stimulate the expression of inducible nitric oxide... 

Siow RC, Li FY, Rowlands DJ, de Winter P, Mann GE. 2007. Cardiovascular targets for estrogens and phytoestrogens Transcriptional regulation of nitric oxide synthase and antioxidant defense genes. Free Radio Biol Med 42 909-925. 

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. 

Tedeschi, E. et al. Green tea inhibits human inducible nitric-oxide synthase expression by down-regulating signal transducer and activator of transcription-1 alpha activation. Mol Pharmacol. 65, 111, 2004. 

Dlaska, M. and Weiss, G. 1999. Central role of transcription factor NF-IL6 for cytokine and iron-mediated regulation of murine inducible nitric oxide synthase expression. J Immunol 162 6171-6177. 

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