title: 1-Bromopropane induces macrophage activation via extracellular signal-regulated kinase 1/2 MAPK and NF-κB pathways.
abstract: 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.
authors.affiliation: BK21 Project Team, Department of Pharmacy, College of Pharmacy and Research Center for Proteineous Materials, Chosun University, Seosuk-dong, Gwangju, Republic of Korea.
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Han
authors.forename: Yong Pil
authors.initials: YP
authors.lastname: Hwang
authors.forename: Kyung Jin
authors.initials: KJ
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; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D005419:Flavonoids / Q000494:pharmacology; D006842:Hydrocarbons, Brominated / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects*; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D015398:Signal Transduction; D013450:Sulfones / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D005419:Flavonoids; D006842:Hydrocarbons, Brominated; D015850:Interleukin-6; D016328:NF-kappa B; D009570:Nitriles; D013450:Sulfones; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D048049:Extracellular Signal-Regulated MAP Kinases; D048052:Mitogen-Activated Protein Kinase 3; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; C118559:1-bromopropane