title: EM, EM703 inhibit NF-kB activation induced by oxidative stress from diesel exhaust particle in human bronchial epithelial cells: importance in IL-8 transcription.
abstract: Diesel exhaust particle (DEP) is the major components of PM2.5, and much attention has focused on PM2.5 in relation to adverse health effects, and many pulmonary diseases. In the present study, we used a human bronchial epithelial cell (HBEC) line to investigate the anti-inflammatory effects of erythromycin (EM) and EM703 - a new derivative of erythromycin without antibacterial effects on the expressions of IL-8 caused by DEP exposure. DEP showed a dose-dependent stimulatory effect on IL-8 product in HBEC. Increases of IL-8 expression by DEP stimulation were significantly blocked by both EM and EM703 pretreatment. Furthermore, NF-κB and Nrf2 activation, the antioxidant enzymes such as HO-1, NQO-1 mRNA expression were increased by DEP exposure and these increases were blocked by both of EM and EM703 pretreatment. Our results suggest that, EM and EM703 may have an inhibitory effect on expression inflammatory cytokines in HBEC induced by DEP not only as an anti-inflammation but also an antioxidant drug. EM and EM703 might contribute to chemical prevention of the risk of pulmonary diseases induced by oxidative stress from environmental pollutant, such as DEP.
authors.affiliation: Department of Hygiene and Public Health, Nippon Medical School, Tokyo 113-8602, Japan. li-yingji@nms.ac.jp
authors.forename: Ying-Ji
authors.initials: YJ
authors.lastname: Li
authors.forename: Takako
authors.initials: T
authors.lastname: Shimizu
authors.forename: Yukiyo
authors.initials: Y
authors.lastname: Hirata
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Inagaki
authors.forename: Hajime
authors.initials: H
authors.lastname: Takizawa
authors.forename: Arata
authors.initials: A
authors.lastname: Azuma
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kawada
authors.forename: Isamu
authors.initials: I
authors.lastname: Sugawara
authors.forename: Shoji
authors.initials: S
authors.lastname: Kudoh
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Sunazuka
authors.forename: Satoshi
authors.initials: S
authors.lastname: Omura
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D016209:Interleukin-8 / Q000096:biosynthesis; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D052638:Particulate Matter / Q000494:pharmacology*; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; C509870:EM703; D018836:Inflammation Mediators; D016209:Interleukin-8; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D052638:Particulate Matter; D001335:Vehicle Emissions; D004917:Erythromycin