title: Melatonin inhibits Prevotella intermedia lipopolysaccharide-induced production of nitric oxide and interleukin-6 in murine macrophages by suppressing NF-κB and STAT1 activity.
abstract: Although a range of biological and pharmacological activities of melatonin have been reported, little is known about its potential anti-inflammatory efficacy in periodontal disease. In this study, we investigated the effects of melatonin on the production of inflammatory mediators by murine macrophages stimulated with lipopolysaccharide (LPS) from Prevotella intermedia, a major cause of inflammatory reactions in the periodontium, and sought to determine the underlying mechanisms of action. Melatonin suppressed the production of nitric oxide (NO) and interleukin-6 (IL-6) at both gene transcription and translation levels in P. intermedia LPS-activated RAW264.7 cells. P. intermedia LPS-induced NF-κB-dependent luciferase activity was significantly inhibited by melatonin. Melatonin did not reduce NF-κB transcriptional activity at the level of IκB-α degradation. Melatonin blocked NF-κB signaling through the inhibition of nuclear translocation and DNA-binding activity of NF-κB p50 subunit and suppressed STAT1 signaling. Although further research is required to clarify the detailed mechanism of action, we conclude that melatonin may contribute to blockade of the host-destructive processes mediated by these two proinflammatory mediators and could be a highly efficient modulator of host response in the treatment of inflammatory periodontal disease.
authors.affiliation: Department of Biological Science, College of Medical and Life Sciences, Silla University, Busan, Korea.
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Choi
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Jin
authors.forename: Ju-Youn
authors.initials: JY
authors.lastname: Lee
authors.forename: Jeom-Il
authors.initials: JI
authors.lastname: Choi
authors.forename: In Soon
authors.initials: IS
authors.lastname: Choi
authors.forename: Sung-Jo
authors.initials: SJ
authors.lastname: Kim
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D018713:Prevotella intermedia / Q000737:chemistry*; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D050794:STAT1 Transcription Factor; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D008550:Melatonin