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首页> 外文期刊>Allergy >Regulation of glucocorticoid receptor in nasal polyps by systemic and intranasal glucocorticoids.
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Regulation of glucocorticoid receptor in nasal polyps by systemic and intranasal glucocorticoids.

机译:全身和鼻内糖皮质激素对鼻息肉中糖皮质激素受体的调节。

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BACKGROUND: Poor response of nasal polyps to glucocorticoids (GCs) may be because of abnormal expression of GC receptors (GR) alpha and beta or to downregulation of GRalpha. We aimed to evaluate the in vivo regulation of GR isoforms in GC-treated nasal polyps and to assess the relationship between clinical response to GCs and GR levels. METHODS: Patients with nasal polyps were randomly (3:1) treated (n = 51) or not (n = 14) with oral prednisone and intranasal budesonide for 2 weeks, plus intranasal budesonide for 10 additional weeks. Nasal symptoms were evaluated. Biopsies were obtained before (w0) and after 2 (w2) and 12 (w12) weeks of treatment, and analysed for their inflammatory content and GR mRNA (10(2) cDNA copies/mug total RNA) and protein (% immunoreactive inflammatory cells) expression. Healthy nasal mucosa (n = 11) was also investigated. Data are presented as median and 25-75th percentile. RESULTS: At w0, nasal polyps expressed less GRalpha mRNA (1343;683-2263; P < 0.05) and GR protein (41;29-54; P < 0.05) than nasal mucosa (2474;1346-2933; 60;51-72, respectively). GRbeta immunoreactivity was higher in nasal polyps (11;4-19; P < 0.05) than in nasal mucosa (5;2-5). At w2, increased GRalpha mRNA (2010;1037-2732; P < 0.01) and GR protein (56;27-71; P = 0.056) were found compared with w0 (1177;759-2058; 37;29-55, respectively). At w12, GRalpha mRNA and GR protein were similar to w0. GRbeta expression was unaltered by treatment. Neither GRalpha nor GRbeta correlated with nasal symptoms. GR immunoreactivity negatively correlated with eosinophils (r = -0.478; P < 0.001). CONCLUSIONS: GRalpha is downregulated in nasal polyps and upregulated by GC treatment. Neither GRalpha nor GRbeta appear to determine the sensitivity to GCs in nasal polyposis.
机译:背景:鼻息肉对糖皮质激素(GC)的不良反应可能是由于GC受体(GR)α和β的异常表达或GRalpha的下调。我们旨在评估GC治疗的鼻息肉中GR同工型的体内调节,并评估对GC的临床反应与GR水平之间的关系。方法:鼻息肉患者随机(3:1)或不(n = 14)接受口服泼尼松和鼻内布地奈德治疗2周,鼻内布地奈德再治疗10周。评估鼻部症状。在治疗前(w0)和治疗后2(w2)和12(w12)周获得活检,并分析其炎性含量,GR mRNA(10(2)cDNA拷贝/杯总RNA)和蛋白质(免疫反应性炎性细胞百分比) )表达。还研究了健康的鼻粘膜(n = 11)。数据表示为中位数和25-75%。结果:在w0时,鼻息肉表达的GRalpha mRNA(1343; 683-2263; P <0.05)和GR蛋白(41; 29-54; P <0.05)比鼻黏膜(2474; 1346-2933; 60; 51- 72)。鼻息肉(11; 4-19; P <0.05)的GRbeta免疫反应性高于鼻黏膜(5; 2-5)。与w0(1177; 759-2058; 37; 29-55)相比,在w2时发现GRalpha mRNA(2010; 1037-2732; P <0.01)和GR蛋白(56; 27-71; P = 0.056)增加。 )。在第12周,GRalpha mRNA和GR蛋白与第0周相似。 GRbeta表达未改变通过治疗。 GRalpha和GRbeta均与鼻症状无关。 GR免疫反应性与嗜酸性粒细胞负相关(r = -0.478; P <0.001)。结论:鼻息肉中GRalpha下调,GC治疗上调。 GRalpha和GRbeta似乎都没有决定鼻息肉对GC的敏感性。

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