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

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. Wi...

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Autores principales:	Agnes E Coutinho, Jeremy K Brown, Fu Yang, David G Brownstein, Mohini Gray, Jonathan R Seckl, John S Savill, Karen E Chapman
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ec5a20e5f24d44f185911da8a047997d
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spelling	oai:doaj.org-article:ec5a20e5f24d44f185911da8a047997d2021-11-18T08:00:49ZMast cells express 11β-hydroxysteroid dehydrogenase type 1: a role in restraining mast cell degranulation.1932-620310.1371/journal.pone.0054640https://doaj.org/article/ec5a20e5f24d44f185911da8a047997d2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23349944/?tool=EBIhttps://doaj.org/toc/1932-6203Mast 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.Agnes E CoutinhoJeremy K BrownFu YangDavid G BrownsteinMohini GrayJonathan R SecklJohn S SavillKaren E ChapmanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e54640 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Agnes E Coutinho Jeremy K Brown Fu Yang David G Brownstein Mohini Gray Jonathan R Seckl John S Savill Karen E Chapman Mast cells express 11β-hydroxysteroid dehydrogenase type 1: a role in restraining mast cell degranulation.
description	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.
format	article
author	Agnes E Coutinho Jeremy K Brown Fu Yang David G Brownstein Mohini Gray Jonathan R Seckl John S Savill Karen E Chapman
author_facet	Agnes E Coutinho Jeremy K Brown Fu Yang David G Brownstein Mohini Gray Jonathan R Seckl John S Savill Karen E Chapman
author_sort	Agnes E Coutinho
title	Mast cells express 11β-hydroxysteroid dehydrogenase type 1: a role in restraining mast cell degranulation.
title_short	Mast cells express 11β-hydroxysteroid dehydrogenase type 1: a role in restraining mast cell degranulation.
title_full	Mast cells express 11β-hydroxysteroid dehydrogenase type 1: a role in restraining mast cell degranulation.
title_fullStr	Mast cells express 11β-hydroxysteroid dehydrogenase type 1: a role in restraining mast cell degranulation.
title_full_unstemmed	Mast cells express 11β-hydroxysteroid dehydrogenase type 1: a role in restraining mast cell degranulation.
title_sort	mast cells express 11β-hydroxysteroid dehydrogenase type 1: a role in restraining mast cell degranulation.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/ec5a20e5f24d44f185911da8a047997d
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Mast cells express 11β-hydroxysteroid dehydrogenase type 1: a role in restraining mast cell degranulation.

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