Effect of melatonin on the generation of nitric oxide in murine macrophages

In the present investigation, the effects of melatonin on the generation of nitric oxide in stimulated murine macrophages were studied by electron paramagnetic resonance techniques, and the underlying mechanisms were discussed. Upon stimulation with lipopolysaccharide/interferon-gamma. macrophages generated a high concentration of nitric oxide. Melatonin pretreatment significantly inhibited the generation of nitric oxide. Western blot and reverse transcription polymerase chain reaction analysis showed that melatonin decreased the expression of inducible nitric oxide synthase at either the protein or mRNA level. Further investigation showed that melatonin significantly attenuated the nitration of cytoplasmic IkappaB-alpha, inhibited the degradation Of IkappaB-alpha, and blocked the translocation of p65/RelA into the nuclei. The results suggest that melatonin inhibits the expression of inducible nitric oxide synthase by modulating the nuclear factor kappaB pathway. (C) 2004 Elsevier B.V. All rights reserved.