Inhibition of the induction of the inducible nitric oxide synthase in murine brain microglial cells by sodium salicylate

Abstract
The induction of the inducible nitric oxide synthase (iNOS) has been proposed to play a role in a variety of inflammatory diseases. Sodium salicylate (NaSal) is the most commonly used anti-inflammatory agent. We investigated whether NaSal can diminish the induction of iNOS in murine brain microglial cells. In primary cultures, interferon-γ (IFN-γ) or lipopolysaccharide (LPS) separately did not stimulate nitric oxide (NO) production, whereas IFN-γ combined with LPS synergistically induced iNOS. NaSal inhibited both the production of NO and expression of iNOS in microglial cells. Synergy between IFN-γ and LPS was mainly dependent on tumour necrosis factor-α (TNF-α) secretion as the increase of the induction of the iNOS by IFN-γ plus LPS was associated with the increase of TNF-α secretion and IFN-γ plus LPS-induced TNF-α secretion by microglial cells was decreased by the treatment with NaSal. These results suggest a possible use of NaSal in managing inflammation of the central nervous system through inhibition of the iNOS induction.