ABSTRACTMacrolide antibiotics are used as anti-inflammatory agents, e.g., for prevention of exacerbations in chronic obstructive pulmonary disease and cystic fibrosis. Several studies have shown improved outcomes after the addition of macrolides to β-lactam antibiotics for treatment of severe community-acquired pneumonia. However, a beneficial effect of macrolides in treating Gram-negative bacterial airway infections, e.g., those caused byPseudomonas aeruginosa, remains to be shown. Macrolide antibiotics have significant side effects, in particular, motility-stimulating activity in the gastrointestinal tract and promotion of bacterial resistance. In this study, EM703, a modified macrolide lacking antibiotic and motility-stimulating activities but with retained anti-inflammatory properties, was used as an adjunct treatment for experimentalP. aeruginosalung infection, in combination with a conventional antibiotic. Airway infections in BALB/cJRj mice were induced by nasal instillation ofP. aeruginosa; this was followed by treatment with the quinolone levofloxacin in the absence or presence of EM703. Survival, inflammatory responses, and cellular influx to the airways were monitored. Both pretreatment and simultaneous administration of EM703 dramatically improved survival in levofloxacin-treated mice withP. aeruginosaairway infections. In addition, EM703 reduced the levels of proinflammatory cytokines, increased the numbers of leukocytes in bronchoalveolar lavage fluid, and reduced the numbers of neutrophils present in lung tissue. In summary, the findings of this study show that the immunomodulatory properties of the modified macrolide EM703 can be important when treating Gram-negative pneumonia, as exemplified byP. aeruginosainfection in this study.

2013-06-01·Pulmonary Pharmacology & Therapeutics3区 · 医学

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

3区 · 医学

Article

作者: Isamu Sugawara ; Yukiyo Hirata ; Ying-Ji Li ; Hajime Takizawa ; Satoshi Omura ; Shoji Kudoh ; Toshiaki Sunazuka ; Hirofumi Inagaki ; Tomoyuki Kawada ; Arata Azuma ; Takako Shimizu

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.

2009-03-01·The Japanese journal of antibiotics

[EM and EM703 suppress inflammatory cytokines formation by human respiratory epithelial cells provoked by diesel exhaust particles].

Article

作者: Ri, Eihi ; Hirata, Yukiyo ; Inagaki, Hirofumi ; Takizawa, Hajime ; Sugawara, Isamu ; Shimizuq, Takako ; Kudo, Shoji ; Omura, Satoshi ; Azuma, Arata ; Kawada, Tomoyuki ; Sunazuka, Toshiaki

100 项与 EM-703 相关的药物交易

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