Areca nut extracts suppress the differentiation and functionality of human monocyte-derived dendritic cells

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.

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.

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.

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.