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Inducible Nitric Oxide Synthase (iNOS)
SIGMA-ALDRICH
Inducible Nitric Oxide Synthase (iNOS)
Macrophages are important for early immune responses to invading microorganisms, and
the production of nitric oxide (NO) is central to this function. NO is generated by inducible
nitric oxide synthase (iNOS, macNOS, Type II NOS) following exposure to certain cytokines,
such as interferon- (IFN-). The IFN- receptor signals through the Janus kinase (JAK)
family and signal transducers and activators of transcription (STAT) proteins. Receptor
occupation and dimerization induces the phosphorylation of associated STATs. Activated
STATs dimerize and translocate to the nucleus where they increase expression of the
transcription factor, IRF-1, that, in turn, binds to specific DNA elements in the iNOS gene
promoter region to increase iNOS gene expression. iNOS is a soluble enzyme that, unlike
eNOS and nNOS, does not require elevated intracellular Ca2+ levels for activation.
References:
Massa, P.T., et al., Increased inducible activation of NF-B and responsive genes in
astrocytes deficient in the protein tyrosine phosphatase SHP-1. J. Interferon Cytokine Res.,
18, 499-507 (1998).
Fehr, T., et al., Crucial role of interferon consensus sequence binding protein, but neither of
interferon regulatory factor 1 nor of nitric oxide synthesis for, protection against murine
listeriosis. J. Exp. Med., 185, 921-931 (1997).