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Published ahead of print on April 24, 2003, doi:10.1165/rcmb.2002-0291OC
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American Journal of Respiratory Cell and Molecular Biology. Vol. 29, pp. 344-351, 2003
© 2003 American Thoracic Society
DOI: 10.1165/rcmb.2002-0291OC

Induction of Regulated upon Activation, Normal T Cells Expressed and Secreted (RANTES) and Transforming Growth Factor-ß1 in Airway Epithelial Cells by Mycoplasma pneumoniae

Azzeddine Dakhama, Monica Kraft, Richard J. Martin and Erwin W. Gelfand

Program in Cell Biology, Departments of Pediatrics and Medicine, National Jewish Medical and Research Center, Denver, Colorado

Address correspondence to: Azzeddine Dakhama, Ph.D., Department of Pediatrics, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206. E-mail: dakhamaa{at}njc.org

Mycoplasma pneumoniae infection exacerbates asthma in children and may play a role in the pathogenesis of chronic asthma. Because the airway epithelium is a preferential site for M. pneumoniae infection and a major source of the chemokine regulated on activation, normal T cells expressed and secreted (RANTES) and transforming growth factor (TGF)-ß1, we postulated that this microorganism may contribute to the disease by inducing these mediators through direct interaction with airway epithelial cells. We investigated the effects of M. pneumoniae on RANTES and TGF-ß1 production in primary cultures of normal human bronchial epithelial (NHBE) cells and small airway epithelial (SAEC) cells. Both cell types were permissive to M. pneumoniae infection in vitro, but their responses were different. TGF-ß1 was induced at higher levels in NHBE than in SAEC cultures, whereas RANTES was induced in SAEC cultures but not in NHBE cultures. These effects were attenuated by erythromycin and dexamethasone. In vitro adherence assays further indicated that the effects of erythromycin were mediated through its antimicrobial action, resulting in diminished adherence of the pathogen, whereas the effects of dexamethasone did not appear to be by inhibition of adherence. These results suggest that M. pneumoniae infection may contribute to the pathogenesis of chronic asthma at different levels of the airways, by inducing TGF-ß1 in large airways and the chemokine RANTES in small airways.

Abbreviations: colony-forming units, cfu • enzyme-linked immunosorbent assay, ELISA • Hanks' balanced salt solution, HBSS • N-2-hydroxyethylpiperazine-N'-ethane sulfonic acid, HEPES • normal human bronchial epithelial cells, NHBE • optical density, O.D. • phosphate-buffered saline, PBS • regulated upon activation, normal T cell expressed and secreted, RANTES • reverse transcription and polymerase chain reaction, RT-PCR • small airway epithelial cells, SAEC • Tris-buffered saline, TBS • transforming growth factor-ß1, TGF-ß1 • tumor necrosis factor, TNF




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