1-Bromopropane induces macrophage activation via extracellular signal-regulated kinase 1/2 MAPK and NF-κB pathways.
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.
Han
Eun Hee
EH
BK21 Project Team, Department of Pharmacy, College of Pharmacy and Research Center for Proteineous Materials, Chosun University, Seosuk-dong, Gwangju, Republic of Korea.
Hwang
Yong Pil
YP
Lee
Kyung Jin
KJ
Jeong
Tae Cheon
TC
Jeong
Hye Gwang
HG
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
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