title: Areca nut extracts increased the expression of cyclooxygenase-2, prostaglandin E2 and interleukin-1α in human immune cells via oxidative stress.
abstract: OBJECTIVE
  Areca nut has been identified as a carcinogen. Inflammation reveals a strong link with tumourigenesis. The aim of this study was to investigate the effects of areca nut on the expression of the key pro-inflammatory mediators involved in malignancy, cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), interleukin (IL)-1α and nuclear factor-κB (NF-κB), by human immune cells. The role of oxidative stress was also examined.
  
  
  METHODS
  Human peripheral blood mononuclear cells (PBMCs) were treated with extracts of ripe areca nut (rANE) or tender areca nut (tANE). Expression of pro-inflammatory mediators was assayed using Western blotting, reverse transcription-polymerase chain reaction, competitive enzyme immunoassay or enzyme-linked immunosorbent assay (ELISA). Activity of NF-κB was evaluated using an ELISA-based method.
  
  
  RESULTS
  Both rANE and tANE enhanced the expression of COX-2, PGE2 and IL-1α by PBMCs. The secretion of PGE2 was induced by rANE (≤20-40μgml(-1)) and tANE (≤160μgml(-1)) significantly in a dose- and time-dependent manner. However, the above enhancing effects of ANEs could be attenuated by antioxidants. ANEs also increased the nuclear expression of the redox-sensitive factor NF-κB.
  
  
  CONCLUSIONS
  The results demonstrate that ANEs induced the expression of pro-inflammatory mediators mainly through the induction of oxidative stress and implicate the possibility of using antioxidants for disease prevention.
authors.affiliation: Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Lien-Yu
authors.initials: LY
authors.lastname: Chang
authors.forename: Hsiao-Ching
authors.initials: HC
authors.lastname: Wan
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Lai
authors.forename: I-Chiang
authors.initials: IC
authors.lastname: Chou
authors.forename: Yen-Ting
authors.initials: YT
authors.lastname: Chen
authors.forename: Shan-Ling
authors.initials: SL
authors.lastname: Hung
mesh_terms: D000328:Adult; D001114:Areca; D015153:Blotting, Western; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D053582:Interleukin-1alpha / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress; D010936:Plant Extracts / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D053582:Interleukin-1alpha; D016328:NF-kappa B; D010936:Plant Extracts; D051546:Cyclooxygenase 2; D015232:Dinoprostone
keywords: ANE; AP-1; AQ; Antioxidant; Areca nut extract; COX-2; Cyclooxygenase-2; ELISA; IL-1α; IL-1β; Interleukin-1α; NF-κB; NSAIDs; OSCC; PBMC; PDTC; PGE(2); Peripheral blood mononuclear cells; Prostaglandin E(2); ROS; RT-PCR; TNF-α; activator protein-1; areca nut extract; areca quid; cyclooxygenase-2; enzyme-linked immunosorbent assay; interleukin-1α; interleukin-1β; nonsteroidal anti-inflammatory drugs; nuclear factor-κB; oral squamous cell carcinoma; peripheral blood mononuclear cells; prostaglandin E(2); pyrrolidine dithiocarbamate; reactive oxygen species; reverse transcription-polymerase chain reaction; tumor necrosis factor-α