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.