Transcription Factors and Inflammatory Lung Disease

Inflammation is a central feature of many lung diseases, including asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis, fibrosing alveolitis and adult or acute respiratory distress syndrome (ARDS). The specific characteristics of the inflammatory response and the site of inflammation differ between these diseases, but all involve the recruitment and activation of inflammatory cells and chances in the structural cells of the lung. These diseases are characterized by an increased expression of many proteins involved in the complex inflammatory cascade. These inflammatory proteins include cytokines, enzymes that produce inflammatory mediators, receptors and adhesion molecules. The increased expression of most of these proteins is the result of increased gene transcription; many of the genes are not expressed in normal cells but are induced in certain cell types in these inflammatory diseases. Changes in gene transcription are regulated by transcription factors, which are proteins that bind to DNA. This suggests that transcription factors may play a key role in the pathophysiology of inflammatory diseases, because they regulate the increased gene expression that may underlie the acute and chronic inflammatory mechanisms that characterize these diseases. Corticosteroids are the most effective therapy in the long-term control of asthma and appear to reduce inflammation in asthmatic airways largely by inhibiting the transcription factors that regulate abnormal gene expression. Corticosteroids may also have a beneficial effect in other inflammatory lung diseases, although this is less marked than in asthma, indicating that different genes and transcription factors are involved.