The molecular and cellular basis of corticosteroid resistance

Abstract

Corticosteroids (CS) can modulate gene expression and are often used to treat a range of immunological and

Glucocorticoid regulation of CD38 expression in human airway smooth muscle cells: role of dual specificity phosphatase 1

“…Glucocorticoids are used in the treatment of many airway inflammatory conditions including asthma (3,4,9). The effects of glucocorticoids in regulating the expression of genes involve the glucocorticoid receptor (GR) (5).…”

Glucocorticoid receptor variants may predispose to rheumatoid arthritis susceptibility

“…GCs exert their action by binding to an intracellular receptor, the glucocorticoid receptor-a (GR-a) (20). The GC/GR-a complex translocates into the nucleus, interacts with GC-responsive elements (GREs) in promoters of target genes and consequently affects their expression.…”

“…The GC/GR-a complex mainly interferes with the binding of transcription factor activator protein (AP)-1 and nuclear factor (NF)-kB to their recognition sites onto a variety of immune regulatory genes such as interleukin (IL)-1, IL-2, IL-3, IL-6, IL-8, TNFa, and many adhesion molecules. In addition, GCs increase the expression of inhibitor (I)-kB, which is an inhibitor of NF-kB, and therefore the latter is maintained in the cytoplasm (20). Furthermore, GCs induce the production of anti-inflammatory proteins such as lipocortin, IL-4, IL-10, IL-13, and transforming growth factor (TGF)-b (20).…”

Adrenal insufficiency and response to corticosteroids in hypotensive critically ill children with cancer

“…Critical illness-related corticosteroid insufficiency is defined as inadequate corticosteroid activity for the severity of the illness of a patient and includes tissuelevel steroid resistance in addition to hypothalamicpituitary axis insufficiency and adrenal gland failure. Tissue corticosteroid resistance is a well-known manifestation of chronic inflammatory diseases such as chronic obstructive pulmonary disease, severe asthma, and systematic lupus erythematosus [19][20][21].…”