Page 15 - Comprehensive treatment of patients with glucocorticoid-dependent severe asthma
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                                Mechanism of action of (systemic) glucocorticoids
Glucocorticoids are steroid hormones secreted by the adrenal cortex in response to inflammatory and stress-related triggers [28]. The first reports describing the use of glucocorticoids for the treatment of patients with asthma are about 70 years old [29-31]. Ever since, there has been an increasing understanding of the mechanisms of glucocorticoids to suppress inflammation [32].
In short, glucocorticoids enter the cell through the plasma membrane, bind to glucocorticoid receptors in the cytoplasm that translocate to the nucleus and lead to changes in gene expression [28;33;34]. These changes can enhance transcription of anti-inflammatory proteins (trans-activation) and also decrease the transcription of pro-inflammatory proteins (trans-repression). Some of the genes with decreased transcription are the ones related to cytokines (IL-1 to IL-6, IL-9, IL-11 to IL-13, IL-16 to IL-18, TNF-alfa), chemokines (IL-8), adhesion molecules (ICAM-1, VCAM-1), inflammatory enzymes (iNOS, inducible COX-2), inflammatory receptors and peptides (endothelin-1) [35;36].
Figure A: Cellular effect of glucocorticoids
Legend to figure 1. Representation of diverse mechanisms of glucocorticoids on inflammatory cells (Adapted with permission from Barnes, 2006 [33])
General introduction and aims of the thesis
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