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. In 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-kappaB (NF-kappaB) 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-kappaB activation.
Chung
C K
CK
Department of Food and Nutrition, Hallym University, ChunChon, South Korea.
Koo
H N
HN
Chung
K Y
KY
Shin
T
T
Kim
H R
HR
Chae
H J
HJ
An
N H
NH
Kim
C H
CH
Kim
H M
HM
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D015153:Blotting, Western; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007371:Interferon-gamma / Q000037:antagonists & inhibitors; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000032:analysis; D011113:Polymyxins / Q000494:pharmacology; D011994:Recombinant Proteins; D012708:Sertoli Cells / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction; D012980:Sodium Salicylate / Q000494:pharmacology*; D019311:Staurosporine / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D016328:NF-kappa B; D009573:Nitrites; D011113:Polymyxins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D019311:Staurosporine; D012980:Sodium Salicylate