Open AccessA Cross-Talk Between NFAT and NF-κB Pathways is Crucial for Nickel- Induced COX-2 Expression in Beas-2B Cells
Author(s) -
Tongjian Cai,
Xueyong Li,
Jin Ding,
Wenjing Luo,
Jingxia Li,
Chuanshu Huang
Publication year - 2011
Publication title -
current cancer drug targets
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.972
H-Index - 91
eISSN - 1873-5576
pISSN - 1568-0096
DOI - 10.2174/156800911795656001
Subject(s) - nfat , nf κb , gene knockdown , reactive oxygen species , chemistry , microbiology and biotechnology , catalase , nfkb1 , signal transduction , cancer research , biology , enzyme , transcription factor , biochemistry , apoptosis , gene
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.