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Cells 2019, 8(2), 112; https://doi.org/10.3390/cells8020112

Suppression of IgE-Independent Degranulation of Murine Connective Tissue-Type Mast Cells by Dexamethasone

1
Department of Immunobiology, Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Tsushima-naka 1-1-1, Kita-ku, Okayama 700-8530, Japan
2
Department of Biomedical Data Intelligence, Graduate School of Medicine, Kyoto University, Shogoin-Kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan
3
Department of Pharmacology, College of Pharmacy, Kinjo Gakuin University, 2-1723 Omori, Moriyama-ku, Nagoya, Aichi 463-8521, Japan
4
Department of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University, Misasagi Nakauchi-cho 5, Yamashina-ku, Kyoto 607-8414, Japan
*
Author to whom correspondence should be addressed.
Received: 29 December 2018 / Revised: 28 January 2019 / Accepted: 31 January 2019 / Published: 1 February 2019
(This article belongs to the Special Issue Mast Cells in Inflammation and Immunity)
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Abstract

Steroidal anti-inflammatory drugs are widely used for the treatment of chronic cutaneous inflammation, such as atopic dermatitis, although it remains unknown how they modulate cutaneous mast cell functions. We investigated the effects of prolonged treatment with a synthetic glucocorticoid, dexamethasone, on murine connective tissue-type mast cells using in vitro and in vivo models. Our connective tissue-type bone marrow-derived cultured mast cell model was found to be sensitive to mast cell secretagogues, such as compound 48/80 and substance P, and higher expression levels of α subunit of a trimeric G protein, Gi1, and several Mas-related G protein-coupled receptor (Mrgpr) subtypes were observed in comparison with immature cultured mast cells. Secretagogue-induced degranulation and up-regulation of these genes was suppressed when cultured in the presence of dexamethasone. The profiles of granule constituents were drastically altered by dexamethasone. Topical application of dexamethasone down-modulated secretagogue-induced degranulation and the expression levels of several Mrgpr subtypes in cutaneous tissue. These results suggest that mast cell-mediated IgE-independent cutaneous inflammation could be suppressed by steroidal anti-inflammatory drugs through the down-regulation of G αi1 and several Mrgpr subtypes in mast cells. View Full-Text
Keywords: mast cell; dexamethasone; trimeric G protein; Mrgpr; skin; inflammation mast cell; dexamethasone; trimeric G protein; Mrgpr; skin; inflammation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Yamada, K.; Sato, H.; Sakamaki, K.; Kamada, M.; Okuno, Y.; Fukuishi, N.; Furuta, K.; Tanaka, S. Suppression of IgE-Independent Degranulation of Murine Connective Tissue-Type Mast Cells by Dexamethasone. Cells 2019, 8, 112.

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