| First Author | Coutinho AE | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 1 | Pages | e54640 |
| PubMed ID | 23349944 | Mgi Jnum | J:195838 |
| Mgi Id | MGI:5486051 | Doi | 10.1371/journal.pone.0054640 |
| Citation | Coutinho AE, et al. (2013) Mast cells express 11beta-hydroxysteroid dehydrogenase type 1: a role in restraining mast cell degranulation. PLoS One 8(1):e54640 |
| abstractText | Mast cells are key initiators of allergic, anaphylactic and inflammatory reactions, producing mediators that affect vascular permeability, angiogenesis and fibrosis. Glucocorticoid pharmacotherapy reduces mast cell number, maturation and activation but effects at physiological levels are unknown. Within cells, glucocorticoid concentration is modulated by the 11beta-hydroxysteroid dehydrogenases (11beta-HSDs). Here we show expression and activity of 11beta-HSD1, but not 11beta-HSD2, in mouse mast cells with 11beta-HSD activity only in the keto-reductase direction, regenerating active glucocorticoids (cortisol, corticosterone) from inert substrates (cortisone, 11-dehydrocorticosterone). Mast cells from 11beta-HSD1-deficient mice show ultrastructural evidence of increased activation, including piecemeal degranulation and have a reduced threshold for IgG immune complex-induced mast cell degranulation. Consistent with reduced intracellular glucocorticoid action in mast cells, levels of carboxypeptidase A3 mRNA, a glucocorticoid-inducible mast cell-specific transcript, are lower in peritoneal cells from 11beta-HSD1-deficient than control mice. These findings suggest that 11beta-HSD1-generated glucocorticoids may tonically restrain mast cell degranulation, potentially influencing allergic, anaphylactic and inflammatory responses. |
