Glucocorticoid suppression of nuclear factor-kappa B: a role for histone modifications.
Corticosteroids are by far the most effective treatment for chronic inflammatory diseases such as asthma. Inflammation in asthma is characterized by the increased expression of multiple inflammatory genes, including those that encode cytokines, chemokines, adhesion molecules, and inflammatory enzymes and receptors. Increased expression of inflammatory genes is regulated by pro-inflammatory transcription factors, such as nuclear factor kappa B (NF-kappa B). These bind to, and activate, co-activator molecules that then acetylate core histones resulting in elevated gene transcription. Corticosteroids reverse histone acetylation at the site of inflammatory gene transcription, either by direct binding of the activated glucocorticoid receptor to NF-kappa B-associated co-activators or by recruitment of histone deacetylases to the activated transcription complex. Understanding how corticosteroids work in asthma may help in designing novel corticosteroids with fewer systemic effects, as well as novel anti-inflammatory approaches.
Kagoshima
M
M
Thoracic Medicine, National Heart & Lung Institute, Imperial College School of Medicine, Dovehouse Street, London SW3 6LY, UK.
Ito
K
K
Cosio
B
B
Adcock
I M
IM
D000107:Acetylation; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D005938:Glucocorticoids / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D006657:Histones; D006877:Hydroxamic Acids; D016328:NF-kappa B; D011500:Protein Synthesis Inhibitors; D011965:Receptors, Glucocorticoid; C012589:trichostatin A