Abstract |
Activation of the transcription factor signal transducer and activator of transcription (STAT)-4 is critical for the differentiation of T-helper 1 cells/type-1 cytotoxic T-cells and the production of interferon (IFN)-gamma. Expression of STAT4, phospho-STAT4, IFN-gamma and T-box expressed in T-cells (T-bet) proteins in bronchial biopsies and bronchoalveolar lavage (BAL)-derived lymphocytes, obtained from 12 smokers with mild/moderate chronic obstructive pulmonary disease ( COPD) (forced expiratory volume in one second (FEV1) 59 +/- 16% predicted), 14 smokers with normal lung function (FEV1 106 +/- 12% pred) and 12 nonsmoking subjects (FEV1 111 +/- 14% pred), was examined by immunohistochemistry and immunocytochemistry. In bronchial biopsies of COPD patients, the number of submucosal phospho-STAT4+ cells was increased (240 (22-406) versus 125 (0-492) versus 29 (0-511) cells mm(-2)) when compared with both healthy smokers and control nonsmokers, respectively. In smokers, phospho-STAT4+ cells correlated with the degree of airflow obstruction and the number of IFN-gamma+ cells. Similar results were seen in BAL (2.8 (0.2-5.9) versus 1.03 (0.09-1.6) versus 0.69 (0-2.3) lymphocytes x mL(-1) x 10(3)). In all smokers who underwent lavage, phospho-STAT4+ lymphocytes correlated with airflow obstruction and the number of IFNgamma+ lymphocytes. T-bet expression was not altered in bronchial biopsies and BAL-derived lymphocytes between the three groups. In conclusion, this study suggests that stable mild/moderate chronic obstructive pulmonary disease is associated with an active T-helper 1 cell/type-1 cytotoxic T-cell inflammatory process involving activation of signal transducer and activator of transcription 4 and interferon-gamma production.
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Authors | A Di Stefano, G Caramori, A Capelli, I Gnemmi, F L Ricciardolo, T Oates, C F Donner, K F Chung, P J Barnes, I M Adcock |
Journal | The European respiratory journal
(Eur Respir J)
Vol. 24
Issue 1
Pg. 78-85
(Jul 2004)
ISSN: 0903-1936 [Print] England |
PMID | 15293608
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- DNA-Binding Proteins
- Inflammation Mediators
- STAT4 Transcription Factor
- STAT4 protein, human
- Trans-Activators
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Topics |
- Aged
- Biopsy, Needle
- Blotting, Western
- Bronchoalveolar Lavage Fluid
(chemistry)
- Bronchoscopy
(methods)
- Case-Control Studies
- Cohort Studies
- DNA-Binding Proteins
(metabolism)
- Female
- Humans
- Immunohistochemistry
- Inflammation Mediators
(analysis, metabolism)
- Male
- Middle Aged
- Pulmonary Disease, Chronic Obstructive
(immunology, pathology)
- Reference Values
- Respiratory Function Tests
- Risk Assessment
- STAT4 Transcription Factor
- Sensitivity and Specificity
- Severity of Illness Index
- Smoking
(immunology, pathology)
- T-Lymphocytes, Helper-Inducer
- Trans-Activators
(metabolism)
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