STAT4 activation in smokers and patients with chronic obstructive pulmonary disease.

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.

• 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)

Chemical References

• DNA-Binding Proteins
• Inflammation Mediators
• STAT4 Transcription Factor
• STAT4 protein, human
• Trans-Activators

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)