This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Google Scholar
Right arrow Articles by Okabayashi, T.
Right arrow Articles by Fujii, N.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Okabayashi, T.
Right arrow Articles by Fujii, N.

 Previous Article  |  Next Article 

Clinical and Vaccine Immunology, June 2009, p. 859-865, Vol. 16, No. 6
1071-412X/09/$08.00+0     doi:10.1128/CVI.00033-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Fosfomycin Suppresses Chemokine Induction in Airway Epithelial Cells Infected with Respiratory Syncytial Virus{triangledown}

Tamaki Okabayashi,1 Shin-ichi Yokota,1 Yuko Yoto,2 Hiroyuki Tsutsumi,2 and Nobuhiro Fujii1*

Department of Microbiology, Sapporo Medical University School of Medicine, S1-W17, Chuou-ku, Sapporo, Hokkaido 060-8556, Japan,1 Department of Pediatrics, Sapporo Medical University School of Medicine, S1-W16, Chuou-ku, Sapporo, Hokkaido 060-8543, Japan2

Received 22 January 2009/ Returned for modification 20 March 2009/ Accepted 9 April 2009

Respiratory syncytial virus (RSV) infects airway epithelial cells, causing bronchiolitis and pneumonia. Inflammation is mediated by various cytokines secreted from RSV-infected airway epithelial cells, and it promotes the pathogenesis of RSV-related diseases. Fosfomycin (FOF) is approved as a treatment for various bacterial infectious diseases, including respiratory infectious diseases, in Japan. FOF is suggested to exhibit immunomodulatory effects on lipopolysaccharide-stimulated monocytes and T lymphocytes, in addition to its antimicrobial activity. We investigated the effect of FOF on the cytokine production of an airway epithelial cell line, A549, infected with RSV. RSV-induced cytokines, such as regulated on activation, normal T-cell expressed and secreted (RANTES), interleukin-8 (IL-8), and IL-6, in infected A549 cells. We found that FOF decreased the levels of RSV-induced RANTES and IL-8 but not the level of RSV-induced IL-6. The RANTES promoter was activated by RSV infection. Site-directed mutagenesis analysis of the RANTES promoter showed that NF-{kappa}B-binding motifs had a critical role in RSV-induced RANTES promoter activity. A luciferase reporter gene assay and a DNA-binding assay indicated that FOF suppressed the NF-{kappa}B activity induced by RSV infection. These results demonstrate that FOF treatment suppresses the RSV-induced transcription of the chemokines RANTES and IL-8 in airway epithelial cells.

* Corresponding author. Mailing address: Department of Microbiology, Sapporo Medical University School of Medicine, S1-W17, Chuou-ku, Sapporo, Hokkaido 060-8556, Japan. Phone: 81-11-611-2111. Fax: 81-11-612-5861. E-mail: fujii{at}sapmed.ac.jp

{triangledown} Published ahead of print on 15 April 2009.

Clinical and Vaccine Immunology, June 2009, p. 859-865, Vol. 16, No. 6
1071-412X/09/$08.00+0     doi:10.1128/CVI.00033-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»