title: Effect of caffeic acid phenethyl ester on Prevotella intermedia lipopolysaccharide-induced production of proinflammatory mediators in murine macrophages.
abstract: OBJECTIVE
  Caffeic acid phenethyl ester (CAPE) has numerous potentially beneficial properties, including antioxidant, immunomodulatory and anti-inflammatory activities. However, the effect of CAPE on periodontal disease has not been studied before. This study was designed to investigate the efficacy of CAPE in ameliorating the production of proinflammatory mediators in macrophages activated by lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen implicated in periodontal disease.
  
  
  METHODS
  LPS from P. intermedia ATCC 25611 was isolated by using the standard hot phenol-water method. Culture supernatants were assayed for nitric oxide (NO), interleukin (IL)-1β and IL-6. We used real-time polymerase chain reaction to quantify inducible NO synthase, IL-1β, IL-6, heme oxygenase (HO)-1 and suppressors of cytokine signaling (SOCS) 1 mRNA expression. HO-1 protein expression and levels of signaling proteins were assessed by immunoblot analysis. DNA-binding activities of NF-κB subunits were analyzed by using the enzyme-linked immunosorbent assay-based kits.
  
  
  RESULTS
  CAPE exerted significant inhibitory effects on P. intermedia LPS-induced production of NO, IL-1β and IL-6 as well as their mRNA expression in RAW264.7 cells. CAPE-induced HO-1 expression in cells activated with P. intermedia LPS, and selective inhibition of HO-1 activity by tin protoporphyrin IX attenuated the inhibitory effect of CAPE on LPS-induced NO production. CAPE did not interfere with IκB-α degradation induced by P. intermedia LPS. Instead, CAPE decreased nuclear translocation of NF-κB p65 and p50 subunits induced with LPS, and lessened LPS-induced p50 binding activity. Further, CAPE showed strong inhibitory effects on LPS-induced signal transducer and activator of transcription 1 and 3 phosphorylation. Besides, CAPE significantly elevated SOCS1 mRNA expression in P. intermedia LPS-stimulated cells.
  
  
  CONCLUSIONS
  Modulation of host response by CAPE may represent an attractive strategy towards the treatment of periodontal disease. In vivo studies are required to appraise the potential of CAPE further as an immunomodulator in the treatment of periodontal disease.
authors.affiliation: Department of Biological Science, College of Medical and Life Sciences, Silla University, Busan, Korea.
authors.forename: E-Y
authors.initials: EY
authors.lastname: Choi
authors.affiliation: Department of Biological Science, College of Medical and Life Sciences, Silla University, Busan, Korea.
authors.forename: S-H
authors.initials: SH
authors.lastname: Choe
authors.affiliation: Department of Biological Science, College of Medical and Life Sciences, Silla University, Busan, Korea.
authors.forename: J-Y
authors.initials: JY
authors.lastname: Hyeon
authors.affiliation: Department of Periodontology, School of Dentistry, Pusan National University, Yangsan, Korea.|Dental Research Institute, Pusan National University Dental Hospital, Yangsan, Korea.
authors.forename: J-I
authors.initials: JI
authors.lastname: Choi
authors.affiliation: Department of Biological Science, College of Medical and Life Sciences, Silla University, Busan, Korea.
authors.forename: I S
authors.initials: IS
authors.lastname: Choi
authors.affiliation: Department of Periodontology, School of Dentistry, Pusan National University, Yangsan, Korea.|Dental Research Institute, Pusan National University Dental Hospital, Yangsan, Korea.|Institute of Translational Dental Sciences, Pusan National University, Yangsan, Korea.
authors.forename: S-J
authors.initials: SJ
authors.lastname: Kim
mesh_terms: D000818:Animals; D002109:Caffeic Acids / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D020869:Gene Expression Profiling; D007155:Immunologic Factors / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000302:isolation & purification / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000378:metabolism; D018713:Prevotella intermedia / Q000737:chemistry; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D002109:Caffeic Acids; D016207:Cytokines; D007155:Immunologic Factors; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009569:Nitric Oxide; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol
keywords: HO-1; NF-κB; SOCS1; STAT; caffeic acid phenethyl ester; lipopolysaccharide; proinflammatory mediators