title: Chlamydia pneumoniae activates epithelial cell proliferation via NF-kappaB and the glucocorticoid receptor.
abstract: Chlamydia pneumoniae is an obligate intracellular eubacterium and a common cause of acute and chronic respiratory tract infections. This study was designed to show the effect of C. pneumoniae on transcription factor activation in epithelial cells. The activation of transcription factors by C. pneumoniae was determined in human epithelial cell lines (HL and Calu3) by electrophoretic DNA mobility shift assay, Western blotting, and luciferase reporter gene assay. The activation of transcription factors was further confirmed by immunostaining of C. pneumoniae-infected HL cells and mock-infected controls. The effect of transcription factors on C. pneumoniae-induced host cell proliferation was assessed by [(3)H]thymidine incorporation and direct cell counting in the presence and absence of antisense oligonucleotides targeting transcription factors or the glucocorticoid receptor (GR) antagonist RU486. The activation of the GR, CCAAT-enhancer binding protein (C/EBP), and NF-kappaB was induced within 1 to 6 h by C. pneumoniae. While the interleukin-6 promoter was not activated by C. pneumoniae, the GR-driven p21((Waf1/Cip1)) promoter was increased 2.5- to 3-fold over controls 24 h after infection. C. pneumoniae dose-dependently increased the DNA synthesis of the host cells 2.5- to 2.9-fold, which was partly inhibited either by RU486 or by NF-kappaB antisense oligonucleotides. Furthermore, we provide evidence that heat-inactivated C. pneumoniae does not cause a significant increase in cell proliferation. Our results demonstrate that C. pneumoniae activates C/EBP-beta, NF-kappaB, and the GR in infected cells. However, only NF-kappaB and the GR were involved in C. pneumoniae-induced proliferation of epithelial cells.
mesh_terms: D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002455:Cell Division; D002460:Cell Line; D002690:Chlamydia Infections / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D016993:Chlamydophila pneumoniae / Q000472:pathogenicity*; D004247:DNA / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D012141:Respiratory Tract Infections / Q000209:etiology / Q000378:metabolism / Q000473:pathology
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D016328:NF-kappa B; D011965:Receptors, Glucocorticoid; D004247:DNA