Suppression of IgE-Independent Degranulation of Murine Connective Tissue-Type Mast Cells by Dexamethasone
Suppression of IgE-Independent Degranulation of Murine Connective Tissue-Type Mast Cells by Dexamethasone
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DOI：
10.3390/cells8020112
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发表时间：
2019-02-01
期刊：
影响因子：
6
通讯作者：
Tanaka, Satoshi
中科院分区：
文献类型：
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作者：
Yamada, Keiko;Sato, Hitomi;Tanaka, Satoshi
类固醇抗炎药被广泛用于治疗慢性皮炎，如特应性皮炎，尽管目前尚不清楚它们如何调节皮肤肥大细胞功能。我们利用体外和体内模型研究了合成糖皮质激素地塞米松长期治疗对小鼠结缔组织肥大细胞的影响。我们的结缔组织型骨髓来源的肥大细胞模型被发现对肥大细胞分泌剂如化合物48/80和P物质敏感，与未成熟的肥大细胞相比，三聚体G蛋白亚基G(I1)和几种Mas相关的G蛋白偶联受体(MRGPR)亚型的表达水平更高。当地塞米松存在时，促分泌剂诱导的脱颗粒和这些基因的上调被抑制。地塞米松显著改变了颗粒成分的分布。局部应用地塞米松下调促分泌剂诱导的脱颗粒及几种mrgpr亚型在皮肤组织中的表达水平。这些结果表明，类固醇抗炎药可通过下调肥大细胞G(I1)和几种MRGPR亚型来抑制肥大细胞介导的IgE非依赖性皮肤炎症。
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 subunit of a trimeric G protein, G(i1), 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 (i1) and several Mrgpr subtypes in mast cells.