title: Induction of regulated upon activation, normal T cells expressed and secreted (RANTES) and transforming growth factor-beta 1 in airway epithelial cells by Mycoplasma pneumoniae.
abstract: 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)-beta1, 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-beta1 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-beta1 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-beta1 in large airways and the chemokine RANTES in small airways.
authors.affiliation: Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA. dakhamaa@njc.org
authors.forename: Azzeddine
authors.initials: A
authors.lastname: Dakhama
authors.forename: Monica
authors.initials: M
authors.lastname: Kraft
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Martin
authors.forename: Erwin W
authors.initials: EW
authors.lastname: Gelfand
mesh_terms: D001249:Asthma / Q000276:immunology* / Q000382:microbiology*; D001980:Bronchi / Q000166:cytology; D002448:Cell Adhesion; D002460:Cell Line; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D004917:Erythromycin / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D009174:Mycoplasma / Q000378:metabolism; D009177:Mycoplasma pneumoniae / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
chemical_list: D018946:Chemokine CCL5; D016207:Cytokines; D017931:DNA Primers; D004731:Endotoxins; D005938:Glucocorticoids; D012333:RNA, Messenger; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D004917:Erythromycin; D003907:Dexamethasone