Beta2-adrenoreceptor agonists and glucocorticosteroids are the two most effective treatments for asthma and are often used in combination. Glucocorticoids mediate their anti-inflammatory effects through the action of activated glucocorticoid receptors (GRs). Many of the effects of GRs on the synthesis of cytokines and other inflammatory mediators are due to a direct interaction with other deoxyribonucleic acid (DNA)-binding proteins belonging to the basic leucine zipper (bZIP) group of transcription factors, such as activator protein-1 (AP-1) and nuclear factor-kappa B (NF-κB). Beta2-agonists are potent bronchodilators at low doses and at high doses can activate gene transcription via a bZIP protein, cyclic adenosine monophosphate (cAMP) response element binding protein (CREB). Activated GRs and CREB can interact with each other within the nucleus to modulate both DNA-binding and gene transcription in either a positive or inhibitory manner, depending on cell type. In lung cells, high doses of β2-agonists reduce the ability of GR to bind DNA, a process which is mediated by CREB activation. Inhibition of GR DNA-binding by CREB raises the possibility that high-dose β2-agonists could have functional antiglucocorticoid activity and may be a basis for the reported increase in asthma morbidity and mortality in industrialized countries, which have increasing per capita β2-agonist use.
CITATION STYLE
Adcock, I. M., Stevens, D. A., & Barnes, P. J. (1996, January). Interactions of glucocorticoids and β2-agonists. European Respiratory Journal. https://doi.org/10.1183/09031936.96.09010160
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