Up-regulation of cyclooxygenase-2 expression by 1-bromopropane in macrophages

Abstract

1-Bromopropane (1-BP) has been used in the workplace as an alternative to ozone-depleting solvents. However, the effect of 1-BP on inflammation is unclear. In the present study, we examined the effect of 1-BP on cyclooxygenase-2 (COX-2) expression and analyzed the molecular mechanism of its activity in murine RAW 264.7 macrophages. 1-BP significantly induced COX-2 protein and mRNA levels, as well as COX-2 promoter-driven luciferase activity and 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. Phosphorylation level of PI3K/Akt, extracellular signal-regulated kinase (ERK) and p38 MAPK phosphorylation were also significantly activated by 1-BP. Taken together, 1-BP has the potential to provide a possibility of inflammation-associated disorders and these findings provide further insight into the signal transduction pathways involved in the inflammatory effects of 1-BP.