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Copyright ©ERS Journals Ltd 2004
STAT4 activation in smokers and patients with chronic obstructive pulmonary disease
1 Salvatore Maugeri Foundation, IRCCS, Medical Centre of Rehabilitation, Division ofPulmonary Disease, Veruno, and 2 OspedaliRiuniti, Bergamo, Italy. 3 Dept of Thoracic Medicine, National Heart and Lung Institute, Imperial College of London, London, UK
CORRESPONDENCE: I.M. Adcock, Dept of Thoracic Medicine, National Heart and Lung Institute, Imperial College of London, Dovehouse Street, London, SW3 6LY, UK. Fax: 44 2073518126. E-mail: ian.adcock@imperial.ac.uk
Keywords: Airway inflammation, chronic obstructive pulmonary disease, signal transducer and activator of transcription 4, T-bet, T-helper 1 cells/type-1 cytotoxic T-cells, T-lymphocytes
Received: July 10, 2003
Accepted March 14, 2004
This work was supported by the Associazione per la Ricerca e la Cura dell'Asma (ARCA; Padova, Italy), Salvatore Maugeri Foundation, IRCCS, "Ricerca Corrente" and GlaxoSmithKline (UK).
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)-
Expression of STAT4, phospho-STAT4, IFN-
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-
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.
. 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. + 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·mL–1x103). In all smokers who underwent lavage, phospho-STAT4+ lymphocytes correlated with airflow obstruction and the number of IFN+ lymphocytes. T-bet expression was not altered in bronchial biopsies and BAL-derived lymphocytes between the three groups.
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