title: 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 E(2) (PGE(2)), 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.
authors.affiliation: Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon, South Korea.
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Han
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Yang
authors.forename: Hyung-Kyun
authors.initials: HK
authors.lastname: Kim
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Choi
authors.forename: Tilak
authors.initials: T
authors.lastname: Khanal
authors.forename: Minh Truong
authors.initials: MT
authors.lastname: Do
authors.forename: Young Chul
authors.initials: YC
authors.lastname: Chung
authors.forename: Kwang Youl
authors.initials: KY
authors.lastname: Lee
authors.forename: Tae Cheon
authors.initials: TC
authors.lastname: Jeong
authors.forename: Hye Gwang
authors.initials: HG
authors.lastname: Jeong
mesh_terms: D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D006842:Hydrocarbons, Brominated / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D006842:Hydrocarbons, Brominated; D016328:NF-kappa B; D014157:Transcription Factors; D051546:Cyclooxygenase 2; D011494:Protein Kinases; C118559:1-bromopropane