Cyclooxygenase-2 induction requires activation of nuclear factor of activated T-cells in Beas-2B cells after vanadium exposure and plays an anti-apoptotic role.
Vanadium, a potent toxic agent and carcinogen, is widely used in industry. Evidences show that exposure to vanadium is associated with an increased risk of lung cancer. But the mechanisms involved are far from fully understood. In this present study, we investigated that exposure of human bronchial epithelial cells (Beas-2B) to vanadium pentoxide resulted in an obvious induction of cyclooxygenase-2 (COX-2) expression and this induction was both dose- and time-dependent. Exposure of Beas-2B cells to vanadium pentoxide also led to significant activation of nuclear factor of activated T-cells (NFAT) on a time- and dose-dependent manner. Furthermore, we found that inhibition of NFAT by dominant negative mutant of NFAT (DN-NFAT) resulted in a dramatic inhibition of COX-2 expression induced by vanadium pentoxide, showing that NFAT activation was required for COX-2 induction by vanadium pentoxide in Beas-2B cells. Moreover, knockdown of COX-2 expression by COX-2-specific small interference RNA and blockage of NFAT pathway by DN-NFAT and NFAT3 small interference RNA showed an increased cell apoptosis in Beas-2B on vanadium exposure. Together, our results demonstrated that COX-2 expression could be induced by vanadium pentoxide in NFAT-dependent way and played an anti-apoptotic role in Beas-2B cells. From the results, we anticipate that the carcinogenesis of vanadium to human bronchial cells may result from anti-apoptosis mediated by the NFAT-dependent induction of COX-2, and we also assume that either pro-apoptotic or anti-apoptotic effect in certain type of cells after vanadium exposure may depend on the level of COX-2 induction.
Tang
Hao
H
Department of Respiratory Disease, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China. tanghao_0921@yahoo.com.cn
Sun
Yu
Y
Xiu
Qingyu
Q
Lu
Huiqi
H
Han
Huanxing
H
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D050778:NFATC Transcription Factors / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*; D014639:Vanadium / Q000008:administration & dosage*
D050778:NFATC Transcription Factors; D014639:Vanadium