title: 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.
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.
  
  
  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.
  
  
  CONCLUSIONS
  Melatonin may be able to prevent diseases induced by oral bacteria.
authors.affiliation: Division of Oral Diagnosis, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado-City, Saitama 350-0283, Japan. ymura@dent.meikai.ac.jp
authors.forename: Yukio
authors.initials: Y
authors.lastname: Murakami
authors.forename: Kenji
authors.initials: K
authors.lastname: Yuhara
authors.forename: Naoki
authors.initials: N
authors.lastname: Takada
authors.forename: Tomoe
authors.initials: T
authors.lastname: Arai
authors.forename: Seiko
authors.initials: S
authors.lastname: Tsuda
authors.forename: Sayako
authors.initials: S
authors.lastname: Takamatsu
authors.forename: Mamoru
authors.initials: M
authors.lastname: Machino
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Fujisawa
mesh_terms: D000818:Animals; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology / Q000633:toxicity; D010861:Fimbriae, Bacterial / Q000276:immunology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007211:Indoles / Q000494:pharmacology / Q000633:toxicity; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology; D008550:Melatonin / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016966:Porphyromonas gingivalis / Q000276:immunology*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D007211:Indoles; D016328:NF-kappa B; C030374:indole; D051546:Cyclooxygenase 2; D008550:Melatonin