Glucocorticoids decrease tissue mast cell number by reducing the production of the c-kit ligand, stem cell factor, by resident cells - In vitro and in vivo evidence in murine systems
Glucocorticoids decrease tissue mast cell number by reducing the production of the c-kit ligand, stem cell factor, by resident cells - In vitro and in vivo evidence in murine systems
复制标题
DOI：
10.1172/jci119336
复制
发表时间：
1997-04-01
影响因子：
15.9
通讯作者：
Metcalfe, DD
中科院分区：
文献类型：
--
作者：
Finotto, S;Mekori, YA;Metcalfe, DD
局部递送糖皮质激素至组织显著减少肥大细胞数量。糖皮质激素的这种药理学作用被认为是糖皮质激素调节过敏性炎症的机制之一。为了确定糖皮质激素能够发挥这种作用的机制，我们首先将糖皮质激素醋酸氟轻松应用于小鼠真皮，并观察到肥大细胞数量的减少与肥大细胞凋亡的增加有关。这似乎不是由于糖皮质激素对肥大细胞的直接作用，因为向干细胞因子（SCF）依赖性肥大细胞培养物中加入0.01-1.0 μ M糖皮质激素地塞米松不会增加肥大细胞死亡。然而，添加地塞米松培养的成纤维细胞的SCF mRNA的下调和SCF蛋白的生产显着减少，同样，免疫组化进行的氟轻松处理的小鼠真皮显示免疫反应性SCF的减少。在醋酸氟轻松给药的真皮部位给予SCF可消除这种糖皮质激素的肥大细胞耗竭作用。因此，糖皮质激素通过下调局部肥大细胞存活所需的组织SCF产生来减少组织肥大细胞数量。这一观察结果可能适用于设计改进的策略来治疗肥大细胞介导的疾病。
The local delivery of glucocorticoids to tissues significantly decreases mast cell number. This pharmacologic effect of glucocorticoids is believed to be one of the mechanisms by which glucocorticoids regulate allergic inflammation. To determine the mechanism by which glucocorticoids are able to exert this effect, we first applied the glucocorticoid fluocinonide to mouse dermis and observed that the decrease in mast cell number was associated with an increase in mast cell apoptosis. This did not appear to be due to a direct effect of the glucocorticoid on mast cells, as the addition of 0.01-1.0 mu M of the glucocorticoid dexamethasone into stern cell factor (SCF)-dependent mast cell cultures did not enhance mast cell death. However, addition of dexamethasone to cultured fibroblasts did result in a downregulation of SCF mRNA and a significant decrease in SCF protein production, Similarly, immunohistochemistry performed on fluocinonide-treated mouse dermis revealed a decrease in immunoreactive SCF. Administration of SCF at sites of fluocinonide administration to the dermis abolished the mast cell-depleting effect of this glucocorticoid. Thus, glucocorticoids decrease tissue mast cell number by downregulating tissue SCF production required for the survival of local mast cells. This observation may be applicable to the design of improved strategies to treat mast cell-mediated disorders.