title: Effects of luteolin on the release of nitric oxide and interleukin-6 by macrophages stimulated with lipopolysaccharide from Prevotella intermedia.
abstract: BACKGROUND
  Although a range of biologic and pharmacologic activities of luteolin has been reported, little is known about its potential as an agent to treat periodontal disease. In the present study, we investigated whether luteolin could downregulate the production of proinflammatory mediators in murine macrophage-like RAW264.7 cells stimulated with lipopolysaccharide (LPS) from Prevotella intermedia (Pi), a major cause of inflammatory periodontal disease, and we attempted to elucidate the possible mechanisms of action.
  
  
  METHODS
  LPS was prepared from lyophilized Pi ATCC 25611 cells by the standard hot phenol-water method. Culture supernatants were collected and assayed for nitric oxide (NO) and interleukin (IL)-6. We used real-time polymerase chain reaction to detect inducible NO synthase (iNOS) and IL-6 mRNA expression. iNOS expression, phosphorylation of JNK and p38, IκB-α degradation, nuclear translocation of nuclear factor-kappaB (NF-κB) subunits, and signal transducer and activator of transcription-1 (STAT1) phosphorylation were characterized via immunoblotting. DNA-binding of NF-κB was also analyzed.
  
  
  RESULTS
  Luteolin strongly suppressed the production of NO and IL-6 at both gene transcription and translation levels in Pi LPS-activated RAW264.7 cells. Mitogen-activated protein kinase pathways were not involved in the inhibition of Pi LPS-induced NO and IL-6 release by luteolin. Luteolin did not reduce NF-κB transcriptional activity at the level of IκB-α degradation. Luteolin blocked NF-κB signaling through inhibition of nuclear translocation and DNA binding activity of NF-κB p50 subunit and suppressed STAT1 signaling.
  
  
  CONCLUSIONS
  Although further research is encouraged to clarify the detailed mechanism of action, flavonoid luteolin may contribute to blockade of the host-destructive processes mediated by these two proinflammatory mediators and could have potential use 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: 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; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D015536:Down-Regulation; D015850:Interleukin-6 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D047311:Luteolin / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010766:Phosphorylation; D018713:Prevotella intermedia / Q000737:chemistry; D060888:Real-Time Polymerase Chain Reaction; D050794:STAT1 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D000093242:Interleukin-6 Inhibitors
chemical_list: D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D008070:Lipopolysaccharides; D047311:Luteolin; D016328:NF-kappa B; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D050794:STAT1 Transcription Factor; D000093242:Interleukin-6 Inhibitors; C494080:Stat1 protein, mouse