Inhibitory effect of sodium salicylate on nitric oxide production from TM4 Sertoli cells

Nitric oxide (NO) 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 production of NO in TM4 Sertoli cells. TM4 Sertoli cells produced a small amount of NO upon treatment with recombinant interferon-gamma (rIFN-gamma). The effect of rIFN-gamma was enhanced markedly by the addition of recombinant TNF-alpha (rTNF-alpha) in a dose-dependent manner. NaSal (10 and 20 mM) significantly inhibited NO production from TM4 Sertoli cells induced by rIFN-gamma plus rTNF-alpha. Tn addition, rIFN-gamma in combination with rTNF-alpha showed a marked increase of the expression of inducible NO synthase (iNOS) protein. Western blot analysis revealed that NaSal (10 and 20 mM) blocked a step of iNOS protein synthesis. The rIFN-gamma plus rTNF-alpha-induced nuclear factor kappa B (NF-kappa B) activation was significantly blocked by NaSal (10 and 20 mM). On the other hand, neither staurosporine nor polymyxin B significantly inhibited NO production from TM4 Sertoli cells induced by rIFN-gamma plus rTNF-alpha. The present results indicate that NaSal inhibits rIFN-gamma plus rTNF-alpha-induced NO production in TM4 Sertoli cells via the signal transduction pathway of NF-kappa B activation. (C) 2000 International Society for Immunopharmacology. Published by Elsevier Science Ltd. All rights reserved.