Suppression of IgE-independent degranulation of murine connective tissue-type mast cells by dexamethasone

Keiko Yamada, Hitomi Sato, Kazuma Sakamaki, Mayumi Kamada, Yasushi Okuno, Nobuyuki Fukuishi, Kazuyuki Furuta, Satoshi Tanaka

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

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 secretagogueinduced 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 Gαi1 and several Mrgpr subtypes in mast cells.

Original languageEnglish
JournalCells
Volume8
Issue number2
DOIs
Publication statusPublished - Feb 2019
Externally publishedYes

Keywords

  • Dexamethasone
  • Inflammation
  • Mast cell
  • Mrgpr
  • Skin
  • Trimeric G protein

ASJC Scopus subject areas

  • Medicine(all)

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