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Nitric oxide inhibits LPS-induced tumor necrosis factor synthesisin vitroandin vivo

Authors
Journal
Life Sciences
0024-3205
Publisher
Elsevier
Publication Date
Volume
59
Issue
13
Identifiers
DOI: 10.1016/0024-3205(96)00425-0
Keywords
  • Murine J774 Macrophages
  • Lipopolysaccharide
  • Tumor Necrosis Factor-α
  • Nitric Oxide
  • Ng-Monomethyl-L-Arginine
  • 3-Morpholinosydnonimine
Disciplines
  • Biology
  • Medicine

Abstract

Abstract The effect of nitric oxide (NO) on LPS-stimulated TNF-α synthesis has been studied in vitro and in vivo. The synthesis of TNF-α in J774 macrophages stimulated with LPS (0.l μg/ml) was increased in concentration-related fashion by NO synthase inhibitor L-NMMA (3-30-300 μM) and reduced by either L-arginine (3-30-300 μM) or the NO donor SIN-1 (1-10-1OOμM). The level of TNF-α in the serum of LPS-challenged rats (6mg/kg/i.p.) was increased in animals pre-treated s.c. with L-NMMA (10 and 50mg/kg) and reduced in those given L- arginine (100 and 300mg/kg). These results show a negative feedback mechanism exhibited by NO on TNF-α synthesis suggesting an important regulatory link between NO and TNF-α in pathological processes.

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