title: Rapid glucocorticoid effects on immune cells.
abstract: Apart from their classic genomic effects, it is well known that glucocorticoids also have rapid, nongenomically mediated effects. Three different mechanisms are currently under discussion as being responsible for these effects: (1) specific interaction with the cytosolic glucocorticoid receptor (cGCR), (2) nonspecific interactions with cellular membranes and (3) specific interactions with membrane-bound glucocorticoid receptors (mGCR). With regard to the first mechanism, there is evidence that although the binding of glucocorticoids to the cGCR-associated multi-protein complex induces the further processes of the classic path, it also leads to a rapid intracellular signalling through other components of the complex (e.g. Src). For the second mechanism, a nonspecific interactive effect with cellular membranes through the intercalation of glucocorticoid molecules is being discussed, which primarily alters cellular functions by influencing cation transport via the plasma membrane and by increasing the proton leak of the mitochondria. With regard to the third, mGCR-mediated mechanism, the first evidence has now been found to suggest a physiological expression of membrane-bound glucocorticoid receptors on human cells, whereas in humans this had previously only been demonstrated on lymphoma cells. The clinical importance and therapeutic relevance of these rapid glucocorticoid effects remains unclear at present, although effects on intracellular signalling, interferences with bioenergetically relevant cell functions and the induction of apoptosis via the mGCR are being discussed. This article gives a detailed presentation of the data available at present concerning rapid glucocorticoid effects on immune cells.
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité University Hospital, Humboldt University, Berlin, Germany. frank.buttgereit@charite.de
authors.forename: Frank
authors.initials: F
authors.lastname: Buttgereit
authors.forename: Alexander
authors.initials: A
authors.lastname: Scheffold
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000737:chemistry*; D005938:Glucocorticoids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D005938:Glucocorticoids; D011956:Receptors, Cell Surface; D011965:Receptors, Glucocorticoid