Preprint Article Version 1 This version is not peer-reviewed

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

Version 1 : Received: 29 December 2018 / Approved: 3 January 2019 / Online: 3 January 2019 (08:55:29 CET)

A peer-reviewed article of this Preprint also exists.

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. 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.

Journal reference: Cells 2019, 8, 112
DOI: 10.3390/cells8020112

Abstract

Steroidal anti-inflammatory drugs are widely used for treatment of chronic cutaneous inflammation, such as atopic dermatitis, although it remains unknown how they modulate cutaneous mast cell functions. Murine connective tissue-type mast cells, which were sensitive to mast cell secretagogues, such as compound 48/80 and substance P, were generated by co-culture of bone marrow-derived mast cells with Swiss 3T3 fibroblasts in the presence of stem cell factor. This process was accompanied by up-regulation of a subunit of a trimeric G protein, Gi1, and several Mas-related G protein-coupled receptor (Mrgpr) subtypes. Secretagogue-induced degranulation and up-regulation of these genes were suppressed when they were cultured in the presence of a synthetic glucocorticoid, dexamethasone. The profiles of granule constituents were drastically altered by dexamethasone. Several Mrgpr subtypes were found to be expressed in the cutaneous tissues and their expression levels were decreased in response to topical application of dexamethasone. The numbers of degranulated cutaneous mast cells in response to compound 48/80 were decreased in mice treated with dexamethasone. These results suggest that mast cell-mediated IgE-independent cutaneous inflammation could be suppressed by steroidal anti-inflammatory drugs through down-regulation of Gai1 and several Mrgpr subtypes in mast cells.

Subject Areas

mast cell; dexamethasone; trimeric G protein; Mrgpr; skin; inflammation

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