title: Areca nut extracts suppress the differentiation and functionality of human monocyte-derived dendritic cells.
abstract: OBJECTIVE
  Areca quid chewing, a major risk factor contributing to the occurrence of oral cancer and precancer, has been reported to be associated with the severity and high prevalence of periodontal diseases in areca quid chewers. As dendritic cells are critically involved in the regulation of innate and adaptive immunity in oral mucosa, the objective of the present study was to investigate the effect of areca nut extracts (ANE) on the differentiation and reactivity of dendritic cells derived from monocytes.
  
  
  METHODS
  Human peripheral blood monocytes were cultured in the presence of granulocyte-monocyte colony-stimulating factor and interleukin-4 for 7 d to generate dendritic cells. To examine the effect of ANE on the generation of dendritic cells, the monocytes were exposed to ANE throughout the 7 d culture period. In addition, the effect of ANE on the maturation of monocyte-derived dendritic cells induced by lipopolysaccharide (LPS) was examined.
  
  
  RESULTS
  Monocytes cultured in granulocyte-monocyte colony-stimulating factor and interleukin-4 exhibited a typical phenotype of dendritic cells, as evidenced by the heightened expression of human leukocyte antigen (HLA)-DR, CD11c and the co-stimulatory molecules CD40, CD80 and CD86. Exposure of the monocytes to ANE did not influence the expression of HLA-DR and CD11c, but markedly attenuated the proportion of CD40-positive cells and the mean fluorescence intensity of CD86. The expression of co-stimulatory molecules in LPS-activated dendritic cells was not affected, whereas the mRNA expression of interleukin-12 induced by LPS was markedly suppressed by ANE treatment in a concentration-dependent manner.
  
  
  CONCLUSIONS
  These results suggest that ANE exposure interfered with the differentiation of dendritic cells from monocytes. Moreover, the functionality of mature monocyte-derived dendritic cells was attenuated in the presence of ANE.
authors.affiliation: School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: C-C
authors.initials: CC
authors.lastname: Wang
authors.forename: T-Y
authors.initials: TY
authors.lastname: Chen
authors.forename: H-Y
authors.initials: HY
authors.lastname: Wu
authors.forename: T-Y
authors.initials: TY
authors.lastname: Liu
authors.forename: T-R
authors.initials: TR
authors.lastname: Jan
mesh_terms: D001114:Areca; D018122:B7-1 Antigen / Q000032:analysis; D051940:B7-2 Antigen / Q000032:analysis; D039521:CD11c Antigen / Q000032:analysis; D019013:CD40 Antigens / Q000032:analysis; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D004396:Coloring Agents; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D018664:Interleukin-12 / Q000032:analysis; D015847:Interleukin-4 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D009754:Nuts; D010641:Phenotype; D010936:Plant Extracts / Q000494:pharmacology* / Q000633:toxicity; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; D039521:CD11c Antigen; D019013:CD40 Antigens; C497964:CD86 protein, human; D004396:Coloring Agents; D006684:HLA-DR Antigens; D008070:Lipopolysaccharides; D010936:Plant Extracts; D013778:Tetrazolium Salts; D013844:Thiazoles; D018664:Interleukin-12; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C022616:thiazolyl blue