Impairment of thymocyte function via induction of apoptosis by areca nut extract.
Areca quid (AQ) chewing is a popular oral habit, especially in Southeast Asia cultures, in which children may be engaged in the addictive habit early in their lives. Extracts of areca nuts, the main component of AQ, have been shown to affect the functionality of T-cells. However, the potential influence of ANE on the development of T-cells is unknown. This study, therefore, investigated the impact of areca nut extracts (ANE) on thymocytes and the potential mechanisms of action. Mice administered intraperitoneally with ANE at 1, 5, or 25 mg/kg daily for 5 days showed significant dose-dependent reductions in thymocyte viability. A marked decrease in the total number of thymocytes and the proportion of thymic CD4(+)CD8(+) cells was observed in the 25 mg ANE/kg-treated mice, whereas the proportion of CD4 and CD8 single positive and CD4(-)CD8(-) cells was significantly increased. Further examination on the functionality of thymocytes showed that ANE suppress IL-2 production both ex vivo and in vitro. These results suggest that ANE may attenuate the development and functionality of thymic T-cells. ANE also directly induced apoptosis in thymic T-cells through activation of casapase-3 and apoptosis inducing factor (AIF). Collectively, the data suggested that the thymus is a sensitive target to ANE. Early exposure to ANE may interfere with the development and functionality of thymic T-cells.
Department of Pathology and Laboratory Medicine, Shin Kong Wu Ho Su Memorial Hospital , Taipei , Taiwan .
Chin-Cheng
CC
Lee
Ying-Chi
YC
Lin
Hsingjin Eugene
HE
Liu
Tong-Rong
TR
Jan
Chia-Chi
CC
Wang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001114:Areca; D007376:Interleukin-2 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010936:Plant Extracts / Q000633:toxicity*; D060168:Thymocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology
D007376:Interleukin-2; D010936:Plant Extracts