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Antimicrobial Agents and Chemotherapy, May 2004, p. 1581-1585, Vol. 48, No. 5
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.5.1581-1585.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Molecular Mechanisms of Anti-Inflammatory Action of Erythromycin in Human Bronchial Epithelial Cells: Possible Role in the Signaling Pathway That Regulates Nuclear Factor-{kappa}B Activation

Masashi Desaki,1* Hitoshi Okazaki,1 Toshiaki Sunazuka,2 Satoshi Omura,2 Kazuhiko Yamamoto,1 and Hajime Takizawa1

Department of Respiratory Medicine, University of Tokyo Graduate School of Medicine,1 Kitasato Medical Institute, Tokyo, Japan2

Received 28 April 2003/ Returned for modification 23 August 2003/ Accepted 21 January 2004

Long-term macrolide therapy has been proven to improve survival in patients with diffuse panbronchiolitis. Although its mechanisms remain unknown, previous studies have suggested the effects of macrolide might be anti-inflammatory rather than antibacterial. To elucidate the molecular mechanisms of its action, we studied here the effects of erythromycin (EM) and its new derivative, EM703, which shows no antibacterial action, on the activation of the transcription factor nuclear factor-{kappa}B (NF-{kappa}B) in human bronchial epithelial cells. Western blotting analysis showed that EM did not inhibit the degradation of I{kappa}B{alpha}, suggesting the molecular target for EM was not the dissociation of NF-{kappa}B from I{kappa}B. An electrophoretic mobility shift assay showed that EM did not interrupt the NF-{kappa}B DNA-binding activity in the nucleus under the conditions tested. Moreover, not only EM but also EM703 suppressed the activation of NF-{kappa}B and the production of interleukin-8, demonstrating that the anti-inflammatory action of the macrolide is independent of its antibacterial activity. Taken together, these data suggest EM has an anti-inflammatory action, presumably via an interaction with the NF-{kappa}B signaling pathway in the downstream of the dissociation from I{kappa}B, resulting in the inhibition of NF-{kappa}B.

* Corresponding author. Mailing address: Department of Respiratory Medicine, University of Tokyo Graduate School of Medicine, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan. Phone: 81-3-3815-5411, x33198. Fax: 81-3-3815-5954. E-mail: desaki-tky{at}umin.ac.jp.

Antimicrobial Agents and Chemotherapy, May 2004, p. 1581-1585, Vol. 48, No. 5
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.5.1581-1585.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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