Mast cells express 11β-hydroxysteroid dehydrogenase type 1: a role in restraining mast cell degranulation
| Autor: | Agnes E. Coutinho, Jonathan R. Seckl, John Savill, Jeremy K. Brown, Mohini Gray, Fu Yang, Karen E. Chapman, David G. Brownstein |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
medicine.medical_specialty
Anatomy and Physiology Carboxypeptidases A Hydrocortisone Cell Degranulation Science Immune Cells Immunology Gene Expression Inflammation Endocrine System Immunoglobulin E Mice Endocrinology Internal medicine 11-beta-Hydroxysteroid Dehydrogenase Type 2 Immune Physiology 11-beta-Hydroxysteroid Dehydrogenase Type 1 Molecular Cell Biology medicine Hypersensitivity Animals Mast Cells Interleukin 5 Anaphylaxis Biology Multidisciplinary biology Allergy and Hypersensitivity Degranulation Mast cell Interleukin 33 medicine.anatomical_structure biology.protein Adrenal Cortex Medicine Clinical Immunology medicine.symptom Cellular Types Corticosterone Glucocorticoid hormones hormone substitutes and hormone antagonists medicine.drug Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 8, Iss 1, p e54640 (2013) |
| ISSN: | 1932-6203 |
| Popis: | 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 11β-HSD activity only in the keto-reductase direction, regenerating active glucocorticoids (cortisol, corticosterone) from inert substrates (cortisone, 11-dehydrocorticosterone). Mast cells from 11β-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 11β-HSD1-deficient than control mice. These findings suggest that 11β-HSD1-generated glucocorticoids may tonically restrain mast cell degranulation, potentially influencing allergic, anaphylactic and inflammatory responses. |
| Databáze: | OpenAIRE |
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