Food and chemical toxicology, 2012-05, Vol.50 (5), p.1616-1622
2012
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- Autor(en) / Beteiligte
- Titel
- 1-Bromopropane up-regulates cyclooxygenase-2 expression via NF-κB and C/EBP activation in murine macrophages
- Ist Teil von
- Food and chemical toxicology, 2012-05, Vol.50 (5), p.1616-1622
- Ort / Verlag
- Oxford: Elsevier Ltd
- Erscheinungsjahr
- 2012
- Quelle
- Elsevier ScienceDirect Journals
- Beschreibungen/Notizen
- ► 1-Bromopropane increased COX-2 expression in macrophages. ► 1-Bromopropane induced NF-κB and C/EBP activation. ► 1-Bromopropane activates Akt/ERK and p38 MAP kinase signaling. ► 1-Bromopropane may modulate inflammatory responses in macrophages. 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0278-6915eISSN: 1873-6351DOI: 10.1016/j.fct.2012.02.006Titel-ID: cdi_crossref_primary_10_1016_j_fct_2012_02_006
- Format
- –
- Schlagworte
- 1-Bromopropane, Akt, Animals, binding proteins, Biological and medical sciences, C/EBP, CCAAT-Enhancer-Binding Proteins - metabolism, Cell Line, COX-2, cyclic AMP, Cyclooxygenase 2 - genetics, Cyclooxygenase 2 - metabolism, gene expression, Gene Expression - drug effects, humans, Hydrocarbons, Brominated - pharmacology, industry, luciferase, macrophages, Macrophages - drug effects, Macrophages - metabolism, MAP kinases, Medical sciences, messenger RNA, metabolites, Mice, mitogen-activated protein kinase, NF-kappa B - metabolism, NF-κB, Polymerase Chain Reaction, Promoter Regions, Genetic, prostaglandin synthase, prostaglandins, Protein Kinases - metabolism, signal transduction, Signal Transduction - drug effects, solvents, Toxicology, transcription factor NF-kappa B, Transcription Factors - genetics, transfection, Up-Regulation - drug effects