title: Caffeic acid phenethyl ester promotes anti-inflammatory effects by inhibiting MAPK and NF-κB signaling in activated HMC-1 human mast cells.
abstract: BACKGROUND
  Caffeic acid phenethyl ester (CAPE), an active component of honeybee propolis, is known to have antioxidant, anti-inflammatory, and other beneficial medicinal properties. However, the molecular mechanisms underlying its anti-allergic effects in mast cells are unknown.
  
  
  OBJECTIVE
  The purpose of the present study was to examine whether CAPE modulates the immunoglobulin E (IgE)-mediated local allergic reaction in animals, as well as to elucidate the effects of CAPE on mast cells in vitro.
  
  
  METHODS
  To investigate the bioactive potential of CAPE (10 or 20 µM), HMC-1 cells were stimulated with phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI) for 24 h in the presence or absence of CAPE. To study the pharmacological effects of CAPE, enzyme-linked immunosorbent assays (ELISAs), RT-PCR, Western blot analysis, electrophoretic mobility shift assays (EMSAs), and fluorescence assays were used.
  
  
  RESULTS
  CAPE (10 mg/kg) inhibited local IgE-mediated allergic reactions (0.164 versus 0.065 O.D.) in a mouse model. Additionally, CAPE (20 µM) attenuated PMACI-stimulated histamine release (3146.42 versus 2564.83 pg/ml) and the production of inflammatory cytokines, such as interleukin (IL)-1β (4.775 versus 0.713 pg/ml, IC50 = 6.67 µM), IL-6 (4771.5 versus 449.1 pg/ml, IC50 = 5.25 µM), and IL-8 (5991.7 versus 2213.1 pg/ml, IC50 = 9.95 µM) in HMC-1 cells. In activated HMC-1 cells, pretreatment with CAPE decreased the phosphorylation of c-Jun N-terminal kinase. In addition, CAPE inhibited PMACI-induced nuclear factor (NF)-κB activation by suppressing IκBα phosphorylation and its degradation.
  
  
  CONCLUSIONS
  Our results indicated that CAPE can modulate mast cell-mediated allergic disease.
authors.affiliation: Department of Dental Hygiene, Choonhae College of Health Sciences , Ulsan , Republic of Korea .
authors.forename: Mi Suk
authors.initials: MS
authors.lastname: Cho
authors.forename: Won Sun
authors.initials: WS
authors.lastname: Park
authors.forename: Won-Kyo
authors.initials: WK
authors.lastname: Jung
authors.forename: Zhong-Ji
authors.initials: ZJ
authors.lastname: Qian
authors.forename: Dae-Sung
authors.initials: DS
authors.lastname: Lee
authors.forename: Jung-Sik
authors.initials: JS
authors.lastname: Choi
authors.forename: Da-Young
authors.initials: DY
authors.lastname: Lee
authors.forename: Sae-Gwang
authors.initials: SG
authors.lastname: Park
authors.forename: Su-Kil
authors.initials: SK
authors.lastname: Seo
authors.forename: Hak-Ju
authors.initials: HJ
authors.lastname: Kim
authors.forename: Jun Yeon
authors.initials: JY
authors.lastname: Won
authors.forename: Byeng Chul
authors.initials: BC
authors.lastname: Yu
authors.forename: Il-Whan
authors.initials: IW
authors.lastname: Choi
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002109:Caffeic Acids / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000187:drug effects; D006632:Histamine / Q000378:metabolism; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D006967:Hypersensitivity / Q000517:prevention & control; D007073:Immunoglobulin E / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002109:Caffeic Acids; D016207:Cytokines; D016328:NF-kappa B; D007073:Immunoglobulin E; D006632:Histamine; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol; D002118:Calcium
keywords: Allergy; cytokine; histamine; immunoglobulin E; passive cutaneous anaphylaxis