Transcription factors in airway diseases

Abstract

Transcription factors regulate the expression of multiple inflammatory genes and play a pivotal role in chronic inflammatory diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Prominent transcription factors in airway diseases include nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1), which together regulate the expression of multiple inflammatory proteins. Glucocorticoids activate glucocorticoid receptors (GR), which act as transcription factors and inhibit transcription induced by NF-kappaB and AP-1. Activation of genes involves hyperacetylation of core histones to open up the chromatin structure to initiate transcription. GR recruit histone deacetylase-2 (HDAC2) to the activated inflammatory gene to switch off transcription. In COPD, there is a marked reduction in HDAC2 expression, resulting in glucocorticoid resistance. Therapeutic implications, which may be generalized to all inflammatory diseases, are discussed.