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Mast cells express 11?-hydroxysteroid dehydrogenase type 1: a role in restraining mast cell degranulation.


ABSTRACT: 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 11?-hydroxysteroid dehydrogenases (11?-HSDs). Here we show expression and activity of 11?-HSD1, but not 11?-HSD2, in mouse mast cells with 11?-HSD activity only in the keto-reductase direction, regenerating active glucocorticoids (cortisol, corticosterone) from inert substrates (cortisone, 11-dehydrocorticosterone). Mast cells from 11?-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 11?-HSD1-deficient than control mice. These findings suggest that 11?-HSD1-generated glucocorticoids may tonically restrain mast cell degranulation, potentially influencing allergic, anaphylactic and inflammatory responses.

SUBMITTER: Coutinho AE 

PROVIDER: S-EPMC3548897 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Mast cells express 11β-hydroxysteroid dehydrogenase type 1: a role in restraining mast cell degranulation.

Coutinho Agnes E AE   Brown Jeremy K JK   Yang Fu F   Brownstein David G DG   Gray Mohini M   Seckl Jonathan R JR   Savill John S JS   Chapman Karen E KE  

PloS one 20130118 1


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 11β-hydroxysteroid dehydrogenases (11β-HSDs). Here we show expression and activity of 11β-HSD1, but not 11β-HSD2, in mouse mast cells with  ...[more]

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