title: Stimulatory effects of areca nut extracts on prostaglandin E2 production by human polymorphonuclear leukocytes.
abstract: BACKGROUND
  Areca quid chewing increases the prevalence of periodontal diseases. Areca nut extract (ANE) inhibits the defensive functions of human polymorphonuclear leukocytes (PMNs). This in vitro study investigates the effects of ANE on the production of cyclooxygenase (COX)-2 and the inflammatory mediator prostaglandin E(2) (PGE(2)) by PMNs.
  
  
  METHODS
  The possible effects of ANE on the production of COX-2 were examined using Western blotting analysis. The viability and production of PGE(2) of treated PMNs were determined using the propidium iodide staining method and the competition enzyme assay, respectively. The possible pathways involved were also examined using the COX-2 inhibitor (NS398), the intracellular calcium chelator 1,2-bis(2-aminophenoxy)ethane-N, N, N', N'-tetraacetic acid tetrakis (acetoxymethyl ester) (BAPTA-AM), the p38 mitogen-activated protein kinase (MAPK) inhibitor (SB203580), and the extracellular signal-regulated protein kinase (ERK) inhibitor (U0126). The effects of ANE on the viability or PGE(2) production were statistically assessed using a one-way analysis of variance and Tukey multiple-comparison intervals with alpha = 0.05.
  
  
  RESULTS
  ANE significantly induced the production of PGE(2) in a time- and concentration-dependent manner. This induction resulted from an increased expression of COX-2. Moreover, the application of BAPTA-AM, SB203580, and U0126 statistically significantly suppressed the induction of PGE(2).
  
  
  CONCLUSIONS
  ANE induced the production of PGE(2). The activation of the intracellular calcium concentrations, p38 MAPK, and ERK may be involved in the inducing effects of ANE on PMNs. The findings suggest that areca nut chewing may induce an inflammatory response and affect the periodontal health of consumers.
authors.affiliation: Department of Stomatology, Taipei Veterans General Hospital, Taipei, Taiwan. yllai@vghtpe.gov.tw
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Lai
authors.forename: Ching-Yi
authors.initials: CY
authors.lastname: Wu
authors.forename: Ya-Yun
authors.initials: YY
authors.lastname: Lee
authors.forename: Hui-Wen
authors.initials: HW
authors.lastname: Chang
authors.forename: Tsung-Yun
authors.initials: TY
authors.lastname: Liu
authors.forename: Shan-Ling
authors.initials: SL
authors.lastname: Hung
mesh_terms: D000328:Adult; D001114:Areca; D015153:Blotting, Western; D002070:Butadienes / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000032:analysis* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D018836:Inflammation Mediators / Q000032:analysis / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000187:drug effects*; D009570:Nitriles / Q000494:pharmacology; D009578:Nitrobenzenes / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D055815:Young Adult; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
chemical_list: D002070:Butadienes; D002614:Chelating Agents; D052246:Cyclooxygenase 2 Inhibitors; D004791:Enzyme Inhibitors; D007093:Imidazoles; D018836:Inflammation Mediators; D009570:Nitriles; D009578:Nitrobenzenes; D010936:Plant Extracts; D011725:Pyridines; D013449:Sulfonamides; C113580:U 0126; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D015232:Dinoprostone; C093642:SB 203580; D002118:Calcium