New insights into the molecular basis of glucocorticoid action

Understanding the molecular mechanisms of glucocorticoid action is a primary step in the development of more effective therapeutic agents. An important part of the anti-inflammatory effects of glucocorticoids in asthma involves repression of the expression of inflammatory mediators, particularly cytokines. The NFκB and AP-1 transcription factors seem to be involved in the expression of a number of crucial target genes in asthma, and there are several possible mechanisms through which glucocorticoids may repress genes regulated by NFκB and AP-1. Recent studies also have demonstrated a significant role for steroid-nuclear receptor coactivators, histone acetylation, and chromatin structure in gene regulation. These newly described mechanisms of gene regulation are discussed in relation to the molecular basis of glucocorticoid action.