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Huang K.-H.,Taipei Medical University | Wang C.-H.,Pulmonary Medicine Research Center | Lin C.-H.,Taipei Medical University | Kuo H.-P.,Pulmonary Medicine Research Center
Journal of Biomedical Science | Year: 2014

Background: Our previous study showed NF-κB repressing factor (NKRF) downregulates IP-10 and IL-8 synthesis in the peripheral blood mononuclear cells and alveolar macrophages of TB patients with high bacterial loads. However, the mechanism underlying the repressive effect of NKRF is not fully understood. Results: The levels of IP-10, IL-8 and NKRF were significantly up-regulated in THP-1 cells treated with heated mycobacterium tuberculosis (H. TB). NKRF inhibited NF-κB-mediated IP-10 and IL-8 synthesis and release induced by H. TB. The repressive effect of NKRF is mediated via interference with NF-κB (p65) binding and RNA polymerase II recruitment to promoter sites of IP-10 and IL-8. Conclusions: We have elucidated that direct contact with MTb induces IP-10, IL-8 and a concomitant increase in NKRF in THP-1 cells. The up-regulated NKRF serves as an endogenous repressor for IP-10 and IL-8 synthesis to hinder host from robust response to MTb infection. © 2014 Huang et al.; licensee BioMed Central.

Punde T.H.,National Tsing Hua University | Wu W.-H.,National Tsing Hua University | Lien P.-C.,National Tsing Hua University | Chang Y.-L.,Pulmonary Medicine Research Center | And 10 more authors.
Integrative Biology (United Kingdom) | Year: 2015

This study reports a biomimetic microsystem that reconstitutes the lung microenvironment for monitoring the role of eosinophil cationic protein (ECP) in lung inflammation. ECP induces the airway epithelial cell expression of CXCL-12, which in turn stimulates the migration of fibrocytes towards the epithelium. This two-layered microfluidic system provides a feasible platform for perfusion culture, and was used in this study to reveal that the CXCL12-CXCR4 axis mediates ECP induced fibrocyte extravasation in lung inflammation. This 'lung-on-a-chip' microdevice serves as a dynamic transwell system by introducing a flow that can reconstitute the blood vessel-tissue interface for in vitro assays, enhancing pre-clinical studies. We made an attempt to develop a new microfluidic model which could not only simulate the transwell for studying cell migration, but could also study the migration in the presence of a flow mimicking the physiological conditions in the body. As blood vessels are the integral part of our body, this model gives an opportunity to study more realistic in vitro models of organs where the blood vessel i.e. flow based migration is involved. This journal is © The Royal Society of Chemistry 2015.

Huang K.-H.,Taipei Medical University | Wang C.-H.,Pulmonary Medicine Research Center | Lee K.-Y.,Pulmonary Medicine Research Center | Lin S.-M.,Pulmonary Medicine Research Center | And 2 more authors.
PLoS ONE | Year: 2013

NF-κB repressing factor (NRF) is a transcriptional silencer implicated in the basal silencing of specific NF-κB targeting genes, including iNOS, IFN-β and IL-8/CXCL8. IP-10/CXCL10 and IL-8/CXCL8 are involved in neutrophil and lymphocyte recruitment against M. tuberculosis (MTb) and disease progression of pulmonary tuberculosis (TB). Alveolar macrophages (AM) and peripheral blood mononuclear cells (PBMC) were used to study the regulatory role of NRF in pulmonary TB. AM and PBMC were purified from 19 TB patients and 15 normal subjects. To study the underlying mechanism, PBMC were exposed to heated TB bacilli. The regulation role of NRF in IP-10/CXCL10 and IL-8/CXCL8 was determined by NRF knock-down or over-expression. NRF binding capabilities in promoter sites were measured by chromatin immunoprecipitation (ChIP) assay. The levels of IP-10/CXCL10, IL-8/CXCL8 and NRF were significantly higher in AM and PBMC in patients with active TB. NRF played an inhibitory role in IP-10/CXCL10 and IL-8/CXCL8 inductions. We delineate the role of NRF in pulmonary TB, which inhibits the expressions of IP-10/CXCL10 and IL-8/CXCL8 in AM and PBMC of patients with high bacterial load. NRF may serve as an endogenous repressor to prevent robust increase in IP-10/CXCL10 and IL-8/CXCL8 when TB bacterial load is high. Copyright: © 2013 Huang et al.

Chen L.-F.,Pulmonary Medicine Research Center | Wang C.-H.,Pulmonary Medicine Research Center | Chou P.-C.,Pulmonary Medicine Research Center | Ho S.-C.,Pulmonary Medicine Research Center | And 3 more authors.
Open Respiratory Medicine Journal | Year: 2012

Background: High-resolution computed tomography (HRCT) has allowed in detection of airway wall abnormalities and emphysema, whose extent may correlate with the clinical severity of the disease in patients with chronic obstructive pulmonary disease (COPD). Six minute walk test (6MWT) and cardiopulmonary exercise test (CPET) can determine functional status. Methods: A study was undertaken to investigate whether the extent of emphysema in COPD patients quantitatively confirmed by HRCT scoring was associated with distance walked, inspiratory capacity (IC) changes after exercise, anaerobic threshold of cardiopulmonary exercise and the BODE index (body mass index, airflow obstruction, dyspnea, exercise performance). Results: Seventeen patients with COPD underwent HRCT scanning, 6MWT and CPET. The emphysema score was highly correlated to forced vital capacity (FVC) (r=-0.748, p<0.001), forced expiratory volume in 1 second (FEV1) (r=-0.615, p<0.01), IC post exercise (r=-0.663, p<0.01) and dyspnea score post exercise (r=0.609, p<0.01), but was not associated with the BODE index. The distance walked during 6MWT was inversely correlated to emphysema score (r=-0.557, p<0.05). IC before exercise was highly related to the 6MWT. The change in IC after exercise was associated with the percent decline of oxygen saturation after exercise (r=0.633, p<0.01). Severity of lung emphysema in COPD patients was inversely correlated to VO2 max (r=-0.514, p<0.05) and anaerobic threshold (r=-0.595, p<0.01) of cardiopulmonary exercise. Conclusions:These results suggest that COPD associated with emphysema on HRCT is characterized by more severe lung function impairment, greater exercise impairment and cardiopulmonary dysfunction. © Ansari et al.

Chou P.-C.,Pulmonary Medicine Research Center | Wang C.-H.,Pulmonary Medicine Research Center | Huang C.-D.,Pulmonary Medicine Research Center | Lo Y.-L.,Pulmonary Medicine Research Center | And 5 more authors.
International Journal of Tuberculosis and Lung Disease | Year: 2012

OBJECTIVE: To determine whether the nucleic acid amplification (NAA) test on specimens collected by bronchoscopy improves the diagnostic accuracy of pulmonary tuberculosis (PTB) in sputum-negative patients. DESIGN: Bronchoscopy was performed among smear-negative PTB suspects to collect respiratory specimens to assess the efficacy and accuracy of the Amplified Mycobacterium Tuberculosis Direct (AMTD) test in the diagnosis of PTB. RESULTS: In 105 PTB suspects, 80 were finally excluded, of whom two were false-AMTD-positive. PTB (n = 25) was diagnosed in 10 patients culture-positive for Mycobacterium tuberculosis (7/105 bronchial wash/ bronchoalveolar lavage [BW/BAL] specimens, 6/315 expectorated sputum specimens [2 positive in 2 patients; 1 positive in 2 patients], and one with both), and in 15 patients with improvement after anti-tuberculosis treatment. Among the 25 PTB patients, 20 were AMTD- positive, of whom four were culture-positive. Three AMTD-negative patients were culture-positive. The sensitivity and specificity of AMTD were respectively 80.0% and 97.5%. The diagnostic yield was higher in respiratory specimens obtained at bronchoscopy and measured by AMTD than in conventional sputum or BW/BAL culture. CONCLUSION: NAA testing on specimens collected using bronchoscopy provides a highly efficient and reliable approach in the diagnosis of PTB in smear-negative PTB suspects. © 2012 The Union.

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