Nitric oxide: an inhibitor of NF-κB/Rel system in glial cells

Nitric oxide (NO) has been reported to regulate NF-kB, one of the best-characterized transcription factors playing important roles in many cellular responses to a large variety of stimuli. NO has been suggested to induce or inhibit the activation of NF-kB, its effect depending, among others, on the cell type considered. In this review, the inhibitory effect of NO on NF-kB (and subsequent suppression of NF-kB-dependent gene expression) in glial cells is reported. In particular, exogenous and endogenous NO has been observed to keep NF-kB suppressed, thus preventing the expression of NF-kB-induced genes, such as inducible NO synthase itself or HIV-1 long terminal repeat. Furthermore, the possible molecular mechanisms of NO-mediated NF-kB inhibition are discussed. More specifically, NO has been reported to suppress NF-kB activation inducing and stabilizing the NF-kB inhibitor, IkB-a. On the other hand, NO may inhibit NF-kB DNA binding through S-nitrosylation of cysteine residue (i.e., Cys62) of the p50 subunit. As a whole, a novel concept that the balance of intracellular NO levels may control the induction of NF-kB in glial cells has been hypothesized.