Abstract
The chronic lung inflammatory activity and carcinogenicity of nickel compounds have been well documented by previous studies from epidemiology both in vitro and in vivo. However, the molecular mechanism involved in nickelinduced chronic lung inflammation is much less understood. The current study demonstrates that exposure of human bronchial epithelial cells (Beas-2B) to nickel compounds results in the induction of the inflammatory cytokine tumor necrosis factor-α (TNF-α) and transactivation of nuclear factor of activated T cells (NFAT), nuclear factor-κB (NF-κB), and activator protein-1 (AP-1). Further studies show that neither overexpression of IKKβ-KM, a kinase inactive mutant of IKKβ, nor the ectopic expression of a dominant negative mutant of NFAT could inhibit the TNF-α induction by nickel exposure. Overexpression of TAM67, a dominant-negative mutant of c-Jun, dramatically reduced the TNF-α induction, suggesting that AP-1 is a mediator of TNF-α induction in nickel responses. Our results show that ERKs are AP-1 upstream kinases responsible for TNF-α induction by nickel exposure; although JNKs, ERKs, and p38K were all activated in the Beas-2B cells exposed to nickel compounds. Our results demonstrate that inflammatory TNF-α could be induced by nickel exposure in Beas-2B cells specifically through an ERKs/AP-1-dependent pathway.
Keywords: Kinase, TNF-α, transcriptional factor, nickel, lung
Current Cancer Drug Targets
Title: TNF-α Induction by Nickel Compounds is Specific Through ERKs/AP-1- Dependent Pathway in Human Bronchial Epithelial Cells
Volume: 9 Issue: 1
Author(s): Jin Ding, Yi Huang, Beifang Ning, Wenfeng Gong, Jingxia Li, Hongyang Wang, Chang-Yan Chen and Chuanshu Huang
Affiliation:
Keywords: Kinase, TNF-α, transcriptional factor, nickel, lung
Abstract: The chronic lung inflammatory activity and carcinogenicity of nickel compounds have been well documented by previous studies from epidemiology both in vitro and in vivo. However, the molecular mechanism involved in nickelinduced chronic lung inflammation is much less understood. The current study demonstrates that exposure of human bronchial epithelial cells (Beas-2B) to nickel compounds results in the induction of the inflammatory cytokine tumor necrosis factor-α (TNF-α) and transactivation of nuclear factor of activated T cells (NFAT), nuclear factor-κB (NF-κB), and activator protein-1 (AP-1). Further studies show that neither overexpression of IKKβ-KM, a kinase inactive mutant of IKKβ, nor the ectopic expression of a dominant negative mutant of NFAT could inhibit the TNF-α induction by nickel exposure. Overexpression of TAM67, a dominant-negative mutant of c-Jun, dramatically reduced the TNF-α induction, suggesting that AP-1 is a mediator of TNF-α induction in nickel responses. Our results show that ERKs are AP-1 upstream kinases responsible for TNF-α induction by nickel exposure; although JNKs, ERKs, and p38K were all activated in the Beas-2B cells exposed to nickel compounds. Our results demonstrate that inflammatory TNF-α could be induced by nickel exposure in Beas-2B cells specifically through an ERKs/AP-1-dependent pathway.
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Cite this article as:
Ding Jin, Huang Yi, Ning Beifang, Gong Wenfeng, Li Jingxia, Wang Hongyang, Chen Chang-Yan and Huang Chuanshu, TNF-α Induction by Nickel Compounds is Specific Through ERKs/AP-1- Dependent Pathway in Human Bronchial Epithelial Cells, Current Cancer Drug Targets 2009; 9 (1) . https://dx.doi.org/10.2174/156800909787313995
DOI https://dx.doi.org/10.2174/156800909787313995 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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