bay-11-7082 and 1-bromopropane

1-Bromopropane (1-BP) has been used in the workplace as an alternative to ozone-depleting solvents. This study examined the effects of 1-BP on the production of nitric oxide (NO) and on proinflammatory cytokines, and analyzed the mechanisms involved in macrophages. 1-BP dose-dependently induced the production of NO and proinflammatory cytokines, such as IL-1β, IL-6, and TNF-α, and expression levels of these genes also increased in a dose-dependent manner. The NF-κB sites were identified in the promoter of the iNOS and proinflammatory cytokine genes. Transient transfection and electrophoretic mobility shift assays revealed that NF-κB-mediated the 1-BP-induced increase in the iNOS and proinflammatory cytokine expression levels. Pretreating the macrophages with the NF-κB inhibitor, BAY 11-7082, and the ERK inhibitor, PD98059, inhibited NO production and iNOS expression induced by 1-BP. This demonstrates that 1-BP stimulates macrophage activation via NF-κB transactivation and ERK1/2 MAP kinase phosphorylation. These results suggest that 1-BP has the potential to be inflammatory and that it has previously unrecognized immunomodulating activity.

Topics: Animals; Cell Line; Dose-Response Relationship, Drug; Extracellular Signal-Regulated MAP Kinases; Flavonoids; Hydrocarbons, Brominated; Interleukin-6; Macrophage Activation; Mice; Mitogen-Activated Protein Kinase 3; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase Type II; Nitriles; Signal Transduction; Sulfones; Tumor Necrosis Factor-alpha