Steroid resistance in nasal polyposis: role of glucocorticoid receptor and TGF-β1
Steroid resistance in nasal polyposis: role of glucocorticoid receptor and TGF-β1
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DOI：
10.4193/rhino11.249
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发表时间：
2012-12-01
期刊：
影响因子：
7.2
通讯作者：
Racca, S.
中科院分区：
文献类型：
--
作者：
Aversa, S.;Ondolo, C.;Racca, S.
背景：糖皮质激素（GC）被认为是治疗鼻息肉（NP）的首选药物。然而，一部分患者即使对高剂量的GC也显示出有限的临床反应。糖皮质激素受体（GR）的表达改变，即GR-α和GR-β，是GC不敏感性的潜在机制。GC调节几种细胞因子的表达，包括转化生长因子-β（TGF-β），这可能有助于NP中的细胞增殖。本研究探讨了GC耐药NPs的一些生物分子特征，并检查了与正常粘膜（NM）可能存在的差异。方法：放射性配体结合试验（结合）用于确定GR-α结合能力; Western印迹法用于评估GR-α，GR-β和TGF-β表达和GR-α亚细胞分布。结果：GR-α存在于NPs和NM中，与NPs中配体的亲和力较低。GR-α普遍存在于结合试验显示GR-α阴性的NP的胞质溶胶中。结论：GR-β和TGF-β 1可能参与了NP的发病过程，但它们在调节GC敏感性中的作用尚不清楚。
Background: Glucocorticoids (GCs) are considered drugs of choice for treating nasal polyps (NPs). However, a subset of patients shows a limited clinical response even to high doses of GCs. Altered expression of glucocorticoid receptors (GRs), namely GR-alpha and GR-beta, is a potential mechanism underlying GC insensitivity. GCs modulate the expression of several cytokines, including transforming growth factor-beta (TGF-beta), which may contribute to cellular proliferation in NPs. The study investigates some biomolecular features of GC-resistant NPs, and examines possible differences from normal mucosa (NM).Methodology: Radioligand binding assay (binding) was used to determine GR-alpha binding capacity; Western blotting was used to evaluate GR-alpha, GR-beta, and TGF-beta expression and GR-alpha subcellular distribution. NPs were sampled in 32 patients during ethmoidectomy; NM was taken from 15 healthy patients during rhinoplasty.Results: GR-alpha was present in NPs and NM, with lower affinity for the ligand in NPs. GR-alpha was prevalent in the cytosol of NPs that were GR-alpha-negative to the binding assay. GR-beta was expressed in NPs and absent in the majority of NM.TGF-beta 1 expression was higher in NPs than in NM.Conclusions: GR-beta and TGF-beta 1 might be involved in NP pathogenesis, but their role in modulating GC sensitivity is still unclear.