Induction of TNFalpha in macrophages by vanadate is dependent on activation of transcription factor NF-kappaB and free radical reactions.

摘要: Vanadium-induced TNFalpha production is believed to play an important role in respiratory disease associated with air pollution and occupational exposure. While vanadium able induce macrophages or airway epithelial cells, the underlying mechanism not well defined. In present study, mechanisms of vanadate-induced were analyzed murine Raw264.7 cells. Vanadate induces a significant amount at both protein mRNA levels, induction vanadate dose-dependent. The analysis was focused on transcriptional regulation gene by vanadate. Transient transfection studies show that promoter activated this activation increase DNA binding activity nuclear factor-kappaB (NF-kappaB). Mutation NF-kappaB site led loss responsiveness vanadate, indicating requirement NF-kappaB. This supported evidence inhibition SN50, specific inhibitor, resulted decrease production. A reactive oxygen species (ROS) explored activity. result shows elevated NADPH, which enhances vanadate-mediated generation ROS, but inhibited antioxidant, N-acetyl-L-cysteine (NAC). Modification enhancement repression NADPH NAC, respectively. Taken together, these results indicate that: (a) contributes production; (b) required for gene; (c) free radical reactions are involved activation.