Role of transcription factors in inflammatory lung diseases

Abstract

Acute and chronic alveolar and/or bronchial inflammation is thought to be central to the pathogenesis of many lung disorders such as asthma, chronic obstructive pulmonary disease (COPD), adult respiratory distress syndrome (ARDS), and idiopathic pulmonary fibrosis (IPF). The site and specific characteristics of the inflammatory responses may be different in each of these diseases, but all are characterised by the recruitment to the lungs and activation of immune and inflammatory cells. These activated cells produce cytokines, oxidants and many other mediators which are involved in inflammation.1 2 Recent data indicate that, in addition, airway epithelial cells are able to act as immune effector cells by secreting pro-inflammatory mediators, oxidants, and cytokines.3 Once triggered, an inappropriate chronic inflammatory response persists in these conditions and is presumed to result in lung injury. The intracellular molecular mechanisms in response to environmental signals, leading to increased gene expression and biosynthesis of proinflammatory mediators by airspace inflammatory and epithelial cells, are of considerable current interest. It is now recognised that there are gene specific factors which regulate the transcription of particular genes by affinity binding to specific recognition motifs, which are usually located in the upstream (5′) promoter region of the gene. These factors, which are usually located in the cytosol, can translocate to the cell nucleus and, by binding to specific consensus sites, can upregulate the rate of transcription of the gene and therefore increase the formation of messenger RNA (mRNA) and the protein of an inflammatory mediator. Some transcription factors are cell specific, but others are ubiquitous. Their activity can be modulated by environmental signals and they may play a key role in immune and inflammatory responses. The transcription factors about which there is most information in immune and inflammatory responses are nuclear factor-kappa (κ)B (NF-κB) and activator protein 1 (AP-1). …