Mast Cells Express 11 beta-hydroxysteroid Dehydrogenase Type 1: A Role in Restraining Mast Cell Degranulation: a role in restraining mast cell degranulation

Agnes E. Coutinho, Jeremy K. Brown, Fu Yang, David G. Brownstein, Mohini Gray, Jonathan R. Seckl, John S. Savill, Karen E. Chapman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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

Original languageEnglish
Article numberARTN e54640
Number of pages8
JournalPLoS ONE
Volume8
Issue number1
DOIs
Publication statusPublished - 18 Jan 2013

Keywords

  • ARTHRITIS
  • ACTIVATION
  • PROMOTES
  • 11-BETA-HSD1
  • GLUCOCORTICOIDS
  • MICE
  • HOMOLOGS
  • PITUITARY-ADRENAL AXIS
  • IN-VIVO
  • INFLAMMATION

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