Chlamydophila pneumoniae enhances secretion of VEGF, TGF-beta and TIMP-1 from human bronchial epithelial cells under Th2 dominant microenvironment

PURPOSE: Chlamydophila pneumoniae infection in the airways is thought to be associated with the pathogenesis of asthma, especially in non-atopic severe asthma with irreversible airway obstruction that may be related to airway remodeling. Here, we investigated whether C. pneumoniae infection enhances the secretion of critical chemical mediators for airway remodeling, such as VEGF, TGF-beta, and TIMP-1, in human bronchial epithelial cells (BECs) in a Th2-dominant microenvironment. METHODS: Human bronchial epithelial cells (BEAS-2B cells) were infected with C. pneumoniae strain TW183 and cultured in both a Th1-dominant microenvironment with INF-gamma and a Th2-dominant microenvironment with IL-4 or IL-13 added to the culture medium. The VEGF, TGF-beta, and TIMP-1 levels in the culture supernatants were measured using enzyme-linked immunosorbent assays (ELISA). The activation of NF-kappaB in each experimental condition was determined using an electrophoretic mobility shift assay. RESULTS: Chlamydophila pneumoniae-infected BECs showed enhanced secretion of VEGF, TGF-beta, and TIMP-1 compared with non-infected BECs. The levels of cytokines secreted from BECs were increased more when IL-13 was added to the culture medium. C. pneumoniae-infected BECs also showed increased NF-kappaB activation. CONCLUSIONS: These results suggest that C. pneumoniae plays a role in the pathogenesis of airway remodeling in asthma, revealing a Th2-dominant immune response. Further studies are required to clarify the precise mechanism of C. pneumoniae infection in airway remodeling.

Increased Expression of Glucocorticoid Receptor beta Messenger RNA in Patients with Ankylosing Spondylitis

BACKGROUND: Glucocorticoids have been known to be less effective for treating ankylosing spondylitis (AS) patients than for treating rheumatoid arthritis (RA) patients. To elucidate the mechanisms underlying this phenomenon, we evaluated whether the glucocorticoid receptor (GR) beta expression of the peripheral blood mononuclear cells (PBMCs) in patients with AS is increased compared with patients with RA. METHODS: PBMCs were isolated from the subjects of 3 study groups: the healthy controls (n=25), the RA patients (n=25), and the AS patients (n=25). All the subjects had never taken corticosteroids and the patients with RA or AS were newly diagnosed. The expression of GR beta messenger RNA (mRNA) was determined by reverse transcription of the total RNA, and this was followed by semi-quantitative polymerase chain reaction analysis (RT-PCR). RESULTS: The level of GR alpha mRNA expression was not different among three groups. GR beta mRNA expression of the AS patients (2.02 [range: 0.99-7.21], median [25th-75th percentiles]) was enhanced compared with that of the controls (0.78 [range: 0.43-1.62]) and the RA patients (0.98 [range: 0.79-1.18]). The level of GR beta mRNA expression was not related to the inflammatory markers or the disease activity score 28 for the RA patients, and it was not related to the Bath ankylosing spondylitis disease activity index for the AS patients. CONCLUSION: The expression of GR beta mRNA, which is a dominant negative regulator for the glucocorticoid response, was increased in AS patients. The results suggest that the increased expression of GR beta mRNA may be related to the ineffectiveness of glucocorticoids for the treatment of AS.

Expression of glucocorticoid receptor beta in peripheral blood mononuclear cells of asthmatics experiencing exacerbation after upper respiratory infection / 천식및알레르기

BACKGROUND AND OBJECTIVES: Glucocorticoids have demonstrated excellent efficacy in decreasing airway inflammation and controlling bronchial asthma symptoms. However, exacerbations of asthma are frequently observed even during treatment with inhaled glucocorticoids, and most of these episodes occur following viral upper respiratory infections (URI). Recently, it has been suggested that transient resistance to glucocorticoid developed after URI and this resistance to glucocorticoid in asthmatics was related to the increased expression of glucocorticoid receptor beta (GCRbeta). The aim of this study is to evaluate the expression of GCRbeta in asthmatics experiencing exacerbation after an episode of URI. METHODS: Peripheral blood mononuclear cells (PBMCs) were obtained from asthmatics experiencing exacerbation after URI (n=15), stable asthmatics (n=23), and normal controls (n= 12). Exacerbated asthmatics were started on systemic glucocorticoids upto two weeks and PBMCs were obtained again after the treatment. The degree of expression of GCRbeta mRNA and ratio of GCRbeta/GCRalpha mRNA were calculated using the semi-quantitative RT-PCR. RESULTS: Compared with stable asthmatics and normal control, exacerbated asthmatics showed significantly higher expression of GCRbeta mRNA and ratio of GCRbeta/GCRalpha mRNA. However, comparing exacerbated asthmatics before and after treatment, we found no significant difference but trends of reduction in expression of GCRbeta mRNA and ratio of GCRbeta/GCRalpha mRNA after treatment. CONCLUSION: These findings suggest that transient resistance to corticosteroid in asthmatics experiencing exacerbation after an episode of URI may be related to increased expression of GCRbeta.