TY - JOUR T1 - Corticosteroid effects on cell signalling JF - European Respiratory Journal JO - Eur Respir J SP - 413 LP - 426 DO - 10.1183/09031936.06.00125404 VL - 27 IS - 2 AU - P. J. Barnes Y1 - 2006/02/01 UR - http://erj.ersjournals.com/content/27/2/413.abstract N2 - Corticosteroids are the most effective anti-inflammatory therapy for asthma. Inflammation in asthma is characterised by the increased expression of multiple inflammatory genes regulated by pro-inflammatory transcription factors, such as nuclear factor-κB and activator protein-1, which bind to and activate coactivator molecules that acetylate core histones and switch on gene transcription. Corticosteroids suppress the multiple inflammatory genes that are activated in asthmatic airways, mainly by reversing histone acetylation of activated inflammatory genes through binding of glucocorticoid receptors to coactivators and recruitment of histone deacetylase 2 to the activated transcription complex. Activated glucocorticoid receptors also bind to recognition sites in the promoters of certain genes in order to activate their transcription, resulting in secretion of anti-inflammatory proteins, such as mitogen-activated protein kinase phosphatase-1, which inhibits mitogen-activated protein kinase signalling pathways. Glucocorticoid receptors may also interact with other recognition sites to inhibit transcription, for example of several genes linked to their side-effects. In some patients with steroid-resistant asthma, there are abnormalities in glucocorticoid receptor signalling pathways. In chronic obstructive pulmonary disease patients and asthmatic patients who smoke, histone deacetylase 2 is markedly impaired as a result of oxidative/nitrative stress, and so inflammation is resistant to the anti-inflammatory effects of corticosteroids. The therapeutic implications of these new findings are discussed. SERIES “SIGNALLING AND TRANSCRIPTIONAL REGULATION IN INFLAMMATORY AND IMMUNE CELLS: IMPORTANCE IN LUNG BIOLOGY AND DISEASE” Edited by K.F. Chung and I.M. Adcock Number 4 in this Series ER -