Chlamydia pneumoniaeActivates Epithelial Cell Proliferation via NF-κB 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-B 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-B 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-␤, NF-B, and the GR in infected cells. However, only NF-B and the GR were involved in C. pneumoniae-induced proliferation of epithelial cells.

Chlamydia pneumoniaeGroEL1 Protein Is Cell Surface Associated and Required for Infection of HEp-2 Cells

“…Activation of NF-B during infection by C. pneumoniae has been described for a variety of different cell types (e.g., epithelial cells, HUVECs, human monocytes, and Mono Mac cells) (22,44,82,83). The activation of NF-B in HUVECs is very fast, as it could be detected within 15 min of infection with C. pneumoniae (44).…”

“…Infection of cultured endothelial cells by C. pneumoniae activates the ubiquitous nuclear factor NF-B, which, upon translocation from the cytosol to the nucleus, up-regulates the expression of a variety of genes involved in inflammatory and proliferative responses (1,15,44). Chlamydiainduced activation of NF-B leads to the up-regulation of genes for tissue factor, E-selectin, and the adhesion molecules ICAM-1 and VCAM-1 (22,40,44,56). We asked whether the surface-localized GroEL1 from C. pneumoniae was the constituent activating NF-B in endothelial cells.…”

Role of the hypothalamic-pituitary-adrenal axis, glucocorticoids and glucocorticoid receptors in toxic sequelae of exposure to bacterial and viral products

“…GR activation leads to increased host cell proliferation, which again can be inhibited by RU486. Thus, in this system, activation of GR ensures the survival and propagation of the infected host cells (Gencay et al 2003). In human peripheral blood mononuclear cells (PBMCs), the bacterial superantigen SEB induces glucocorticoid resistance in T cells by increasing the expression of the proposed dominant negative GR isoform, GR (Hauk et al 2000).…”

Chlamydia pneumoniae Infection in Polarized Epithelial Cell Lines

“…The Calu-3 cell line is reported to form a strong functional barrier in a polarized culture (6,37). Both cell lines have previously been shown to be susceptible to C. pneumoniae infection when grown on impermeable supports (9,42). The purpose of the present study was to characterize C. pneumoniae infection in filtergrown/polarized cultures of respiratory epithelial cells.…”