Abstract
Cyclooxygenase-2 (COX-2) is a critical enzyme implicated in chronic inflammation-associated cancer development. Our studies have shown that the exposure of Beas-2B cells, a human bronchial epithelial cell line, to lung carcinogenic nickel compounds results in increased COX-2 expression. However, the signaling pathways leading to nickel-induced COX-2 expression are not well understood. In the current study, we found that the exposure of Beas-2B cells to nickel compounds resulted in the activation of both nuclear factor of activated T cell (NFAT) and nuclear factor- κB (NF-κB). The expression of COX-2 induced upon nickel exposure was inhibited by either a NFAT pharmacological inhibitor or the knockdown of NFAT3 by specific siRNA. We further found that the activation of NFAT and NF-κB was dependent on each other. Since our previous studies have shown that NF-κB activation is critical for nickel-induced COX- 2 expression in Beas-2B cells exposed to nickel compounds under same experimental condition, we anticipate that there might be a cross-talk between the activation of NFAT and NF-κB for the COX-2 induction due to nickel exposure in Beas-2B cells. Furthermore, we showed that the scavenging of reactive oxygen species (ROS) by introduction of mitochondrial catalase inhibited the activation of both NFAT and NF-κB, and the induction of COX-2 due to nickel exposure. Taken together, our results defining the evidence showing a key role of the cross-talk between NFAT and NF- κB pathways in regulating nickel-induced COX-2 expression, further provide insight into the understanding of the molecular mechanisms linking nickel exposure to its lung carcinogenic effects.
Keywords: Beas-2B cells, COX-2, nickel, NFAT, NF-κB, ROS, activator protein-1, dichlorofluorescein diacetate, Cyclosporine A, mouse embryonic fibroblasts, sodium dodecyl sulfate, vascular endothelial growth factor, urokinase-type plasminogen activator
Current Cancer Drug Targets
Title: A Cross-Talk Between NFAT and NF-κB Pathways is Crucial for Nickel- Induced COX-2 Expression in Beas-2B Cells
Volume: 11 Issue: 5
Author(s): T. Cai, X. Li, J. Ding, W. Luo, J. Li and C. Huang
Affiliation:
Keywords: Beas-2B cells, COX-2, nickel, NFAT, NF-κB, ROS, activator protein-1, dichlorofluorescein diacetate, Cyclosporine A, mouse embryonic fibroblasts, sodium dodecyl sulfate, vascular endothelial growth factor, urokinase-type plasminogen activator
Abstract: Cyclooxygenase-2 (COX-2) is a critical enzyme implicated in chronic inflammation-associated cancer development. Our studies have shown that the exposure of Beas-2B cells, a human bronchial epithelial cell line, to lung carcinogenic nickel compounds results in increased COX-2 expression. However, the signaling pathways leading to nickel-induced COX-2 expression are not well understood. In the current study, we found that the exposure of Beas-2B cells to nickel compounds resulted in the activation of both nuclear factor of activated T cell (NFAT) and nuclear factor- κB (NF-κB). The expression of COX-2 induced upon nickel exposure was inhibited by either a NFAT pharmacological inhibitor or the knockdown of NFAT3 by specific siRNA. We further found that the activation of NFAT and NF-κB was dependent on each other. Since our previous studies have shown that NF-κB activation is critical for nickel-induced COX- 2 expression in Beas-2B cells exposed to nickel compounds under same experimental condition, we anticipate that there might be a cross-talk between the activation of NFAT and NF-κB for the COX-2 induction due to nickel exposure in Beas-2B cells. Furthermore, we showed that the scavenging of reactive oxygen species (ROS) by introduction of mitochondrial catalase inhibited the activation of both NFAT and NF-κB, and the induction of COX-2 due to nickel exposure. Taken together, our results defining the evidence showing a key role of the cross-talk between NFAT and NF- κB pathways in regulating nickel-induced COX-2 expression, further provide insight into the understanding of the molecular mechanisms linking nickel exposure to its lung carcinogenic effects.
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Cai T., Li X., Ding J., Luo W., Li J. and Huang C., A Cross-Talk Between NFAT and NF-κB Pathways is Crucial for Nickel- Induced COX-2 Expression in Beas-2B Cells, Current Cancer Drug Targets 2011; 11 (5) . https://dx.doi.org/10.2174/156800911795656001
DOI https://dx.doi.org/10.2174/156800911795656001 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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