The relationship of the transcription factors AP-1 and NF-KB with lung function in the lungs of patients with chronic obstructive pulmonary disease

A. J. Crowther, I. Rahman, W. MacNee (Edinburgh, United Kingdom)

Source: Annual Congress 2001 - Inflammation and genetics in airway disease
Session: Inflammation and genetics in airway disease
Session type: Oral Presentation
Number: 3384
Disease area: Airway diseases

Congress or journal article abstract

Abstract

Chronic obstructive pulmonary disease (COPD) is a common smoking related disorder. An oxidant/antioxidant imbalance may exist in the lung environment in COPD.Activation of redox sensitive transcription factors AP-1 and NF-κB may be important in the development of Inflammation in COPD. We investigated the levels of NF-κB and AP-1 in peripheral lung tissue, and compared levels with spirometry (forced expiratory volume in one second (FEV1), and smoking history. Fresh lung tissue was obtained form 18 patients undergoing lung volume rduction surgery, or lung resection for a suspected peripheral bronchial carcinoma. Nuclear protein was extracted from the lung tissue and the DNA binding of AP-1 and NF-κB and OCT-1 was measured using th electromobility gel shift assay. The relationship of percent predicted FEV1 with AP-1 DNA binding showed a negative correlation of r=-0.11 (p=0.68) and when expressed as a ratio of AP-1 to OCT-1 binding showed a negative correlation of r=-0.43, p=0.076. No correaltion was demonstrated between percent predicted FEV1 and NF-κB DNA binding (r=0.1,p=0.69), and no correaltion between percent predicted FEV1 and the ratio of NF-κB/OCT-1 (R=0.26, P=0.294). Our results demonstrate elevated levels of AP-1 DNA binding in subjects with COPD. This suggests a potential role of AP-1 in enhanced inflammatory response and progressive decline in FEV1 in COPD.
Supported by Cunninghan Trust and Novartis,UK.


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A. J. Crowther, I. Rahman, W. MacNee (Edinburgh, United Kingdom). The relationship of the transcription factors AP-1 and NF-KB with lung function in the lungs of patients with chronic obstructive pulmonary disease. Eur Respir J 2001; 16: Suppl. 31, 3384

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