EM, EM703 inhibit NF-kB activation induced by oxidative stress from diesel exhaust particle in human bronchial epithelial cells: Importance in IL-8 transcription - 22/01/13

Doi : 10.1016/j.pupt.2012.12.010

Ying-Ji Li ^a,^⁎ , Takako Shimizu ^a, Yukiyo Hirata ^a, Hirofumi Inagaki ^a, Hajime Takizawa ^b, Arata Azuma ^c, Tomoyuki Kawada ^a, Isamu Sugawara ^d, Shoji Kudoh ^c,^e, Toshiaki Sunazuka ^f, Satoshi Omura ^f
^a Department of Hygiene and Public Health, Nippon Medical School, Tokyo 113-8602, Japan
^b Department of Respiratory Medicine, Kyorin University Hospital, Tokyo, Japan
^c Department of Pulmonary Medicine/Infection and Oncology, Nippon Medical School, Tokyo, Japan
^d Mycobacterial Reference Center, The Research Institute of Tuberculosis, Tokyo, Japan
^e Anti-Tuberculosis Association, Fukujuji Hospital, Tokyo, Japan
^f Institute for Life Sciences, Kitasato University, Tokyo, Japan

Corresponding author. Tel.: +81 3 3822 2131; fax: +81 3 5685 3065.

Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Tuesday 22 January 2013

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.

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Keywords : Diesel exhaust particle (DEP), Human bronchial epithelial cells, IL-8, Oxidative stress, NF-kB, EM/EM703