Effect of melatonin on cyclooxygenase-2 expression and nuclear factor-kappa B activation in RAW264.7 macrophage-like cells stimulated with fimbriae of Porphyromonas gingivalis

In Vivo. 2011 Jul-Aug;25(4):641-7.

Abstract

Background: The possible link between melatonin and anti-inflammatory activity is currently a focus of interest. In the present study, COX-2 expression and NF-κB activation in RAW264.7 macrophage-like cells stimulated with the fimbriae of Porphyromonas gingivalis, an oral anaerobe, in the absence and presence of melatonin were investigated.

Materials and methods: The cytotoxicity of melatonin and indole against RAW264.7 cells was determined using a cell counting kit. The regulatory effect of melatonin, and of indole on the expression of COX-2 mRNA stimulated by exposure to the fimbriae was investigated by Northern blot analysis. NF-κB activation was evaluated by both electrophoretic mobility-shift assay and Western blot analysis.

Results: The half maximal (50%) effective concentration (EC(50)) values for melatonin and indole were 3300 μM and 130 μM, respectively. Melatonin at non-cytotoxic concentrations significantly inhibited the fimbria-induced expression of COX-2. The fimbria-stimulated binding of NF-κB to its consensus sequence and phosphorylation-dependent proteolysis of inhibitor κB-α were markedly inhibited by melatonin. However, indole did not inhibit COX-2 expression and NF-κB activation.

Conclusion: Melatonin may be able to prevent diseases induced by oral bacteria.

MeSH terms

  • Animals
  • Cell Line
  • Cyclooxygenase 2 Inhibitors / pharmacology
  • Cyclooxygenase 2 Inhibitors / toxicity
  • Cyclooxygenase 2* / genetics
  • Cyclooxygenase 2* / metabolism
  • Fimbriae, Bacterial / immunology*
  • Gene Expression Regulation / drug effects*
  • Humans
  • Indoles / pharmacology
  • Indoles / toxicity
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Macrophages / microbiology
  • Melatonin / chemistry
  • Melatonin / pharmacology*
  • Melatonin / toxicity
  • Mice
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism*
  • Porphyromonas gingivalis / immunology*

Substances

  • Cyclooxygenase 2 Inhibitors
  • Indoles
  • NF-kappa B
  • indole
  • Cyclooxygenase 2
  • Melatonin