Increased glucocorticoid receptor β in airway cells of glucocorticoid-insensitive asthma
Increased glucocorticoid receptor β in airway cells of glucocorticoid-insensitive asthma
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DOI：
10.1164/ajrccm.159.5.9804131
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发表时间：
1999-05-01
影响因子：
24.7
通讯作者：
Leung, DYM
中科院分区：
文献类型：
--
作者：
Hamid, QA;Wenzel, SE;Leung, DYM
糖皮质激素（GC）不敏感哮喘是一个具有挑战性的临床问题，可能与危及生命的疾病进展有关。GC不敏感的分子基础尚不清楚。GC受体（GCR）前mrna的选择性剪接产生第二种GCR，称为GCR β，它不结合GC，但拮抗经典GCR的反激活活性。因此，GCR β的表达增加可能是糖皮质激素不敏感的原因。采用GCR β特异性抗体免疫组化染色法检测支气管肺泡破坏细胞（BAL）和外周血单核细胞（PBMC）的GCR β免疫反应性。使用双免疫染色技术进行GCR β表达的细胞定位。gc不敏感哮喘患者在BAL和外周血中表达的GCR β免疫反应细胞数量明显高于gc敏感哮喘患者或正常对照组。此外，GCR β在gc不敏感哮喘中的表达在气道T细胞中特别高，这被认为在哮喘的发病机制中起主要作用。我们还检测了慢性支气管炎患者气道标本中GCR β的表达。在慢性支气管炎中，很少有细胞呈GCR β阳性，其数量与正常对照组无显著差异。我们得出结论，gc不敏感哮喘与气道T细胞中GCR β表达增加有关。
Glucocorticoid (GC)-insensitive asthma is a challenging clinical problem that can be associated with life-threatening disease progression. The molecular basis of GC insensitivity is unknown. Alternative splicing of the GC receptor (GCR) pre-mRNA generates a second GCR, termed GCR beta, which does not bind GC but antagonizes the transactivating activity of the classic GCR. Thus increased expression of GCR beta could account for glucocorticoid insensitivity. Bronchoalveolar ravage (BAL) cells and peripheral blood mononuclear cells (PBMC) were examined for GCR beta immunoreactivity using a GCR beta-specific antibody by immunohistochemical staining. Cell localization of GCR beta expression was performed using a double immunostaining technique. Patients with GC-insensitive asthma expressed a significantly higher number of GCR beta-immunoreactive cells in their BAL and peripheral blood than GC-sensitive asthmatics or normal control subjects. Furthermore, GCR beta expression in GC-insensitive asthma was particularly high in airway T cells, which are thought to play a major role in the pathogenesis of asthma. We also examined the expression of GCR beta in specimens from the airways of patients with chronic bronchitis. In chronic bronchitis, few cells were GCR beta-positive and their numbers did not differ significantly from normal control subjects. We conclude that GC-insensitive asthma is associated with increased expression of GCR beta in airway T cells.