1-Bromopropane up-regulates cyclooxygenase-2 expression via NF-κB and C/EBP activation in murine macrophages

Abstract

1-Bromopropane (1-BP) has been used in industry as an alternative to ozone-depleting solvents. In the present study, we examined the effect of 1-BP on cyclooxygenase-2 (COX-2) gene expression and analyzed the molecular mechanism of its activity in murine RAW 264.7 macrophages. 1-BP dose-dependently increased COX-2 protein and mRNA levels, as well as COX-2 promoter-driven luciferase activity in macrophages. Additionally, exposure to 1-BP markedly enhanced the production of prostaglandin E2 (PGE2), a major COX-2 metabolite, in macrophages. Transfection experiments with several human COX-2 promoter constructs revealed that 1-BP activated the transcription factors nuclear factor-κB (NF-κB) and CCAAT/enhancer-binding protein (C/EBP), but not AP-1 or the cyclic AMP response element binding protein. Furthermore, Akt and mitogen-activated protein (MAP) kinases were significantly activated by 1-BP. These results demonstrated that 1-BP induced COX-2 expression via NF-κB and C/EBP activation through the Akt/ERK and p38 MAP kinase pathways. These findings provide further insight into the signal transduction pathways involved in the inflammatory effects of 1-BP.