Suppression of IgE-Independent Degranulation of Murine Connective Tissue-Type Mast Cells by Dexamethasone
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, dexametha...
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MDPI AG
2019-02-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/8/2/112 |
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| author | Keiko Yamada Hitomi Sato Kazuma Sakamaki Mayumi Kamada Yasushi Okuno Nobuyuki Fukuishi Kazuyuki Furuta Satoshi Tanaka |
| author_facet | Keiko Yamada Hitomi Sato Kazuma Sakamaki Mayumi Kamada Yasushi Okuno Nobuyuki Fukuishi Kazuyuki Furuta Satoshi Tanaka |
| author_sort | Keiko Yamada |
| collection | DOAJ |
| description | 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, G<sub>i1</sub>, 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 <sub>αi1</sub> and several Mrgpr subtypes in mast cells. |
| first_indexed | 2024-03-12T19:56:11Z |
| format | Article |
| id | doaj.art-a7c98187753f4c9c99fa058d841335bc |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T19:56:11Z |
| publishDate | 2019-02-01 |
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| spelling | doaj.art-a7c98187753f4c9c99fa058d841335bc2023-08-02T02:49:46ZengMDPI AGCells2073-44092019-02-018211210.3390/cells8020112cells8020112Suppression of IgE-Independent Degranulation of Murine Connective Tissue-Type Mast Cells by DexamethasoneKeiko Yamada0Hitomi Sato1Kazuma Sakamaki2Mayumi Kamada3Yasushi Okuno4Nobuyuki Fukuishi5Kazuyuki Furuta6Satoshi Tanaka7Department 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, JapanDepartment 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, JapanDepartment 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, JapanDepartment of Biomedical Data Intelligence, Graduate School of Medicine, Kyoto University, Shogoin-Kawaharacho, Sakyo-ku, Kyoto 606-8507, JapanDepartment of Biomedical Data Intelligence, Graduate School of Medicine, Kyoto University, Shogoin-Kawaharacho, Sakyo-ku, Kyoto 606-8507, JapanDepartment of Pharmacology, College of Pharmacy, Kinjo Gakuin University, 2-1723 Omori, Moriyama-ku, Nagoya, Aichi 463-8521, JapanDepartment 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, JapanDepartment of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University, Misasagi Nakauchi-cho 5, Yamashina-ku, Kyoto 607-8414, JapanSteroidal 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, G<sub>i1</sub>, 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 <sub>αi1</sub> and several Mrgpr subtypes in mast cells.https://www.mdpi.com/2073-4409/8/2/112mast celldexamethasonetrimeric G proteinMrgprskininflammation |
| spellingShingle | Keiko Yamada Hitomi Sato Kazuma Sakamaki Mayumi Kamada Yasushi Okuno Nobuyuki Fukuishi Kazuyuki Furuta Satoshi Tanaka Suppression of IgE-Independent Degranulation of Murine Connective Tissue-Type Mast Cells by Dexamethasone Cells mast cell dexamethasone trimeric G protein Mrgpr skin inflammation |
| title | Suppression of IgE-Independent Degranulation of Murine Connective Tissue-Type Mast Cells by Dexamethasone |
| title_full | Suppression of IgE-Independent Degranulation of Murine Connective Tissue-Type Mast Cells by Dexamethasone |
| title_fullStr | Suppression of IgE-Independent Degranulation of Murine Connective Tissue-Type Mast Cells by Dexamethasone |
| title_full_unstemmed | Suppression of IgE-Independent Degranulation of Murine Connective Tissue-Type Mast Cells by Dexamethasone |
| title_short | Suppression of IgE-Independent Degranulation of Murine Connective Tissue-Type Mast Cells by Dexamethasone |
| title_sort | suppression of ige independent degranulation of murine connective tissue type mast cells by dexamethasone |
| topic | mast cell dexamethasone trimeric G protein Mrgpr skin inflammation |
| url | https://www.mdpi.com/2073-4409/8/2/112 |
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