Molecular analysis of effects of gtucocorticoids on eosinophilic rhinosinusitis with reference to regulation of inflammatory transcription factors.

最近的研究表明嗜酸性粒细胞在非感染性慢性鼻窦炎的持续炎症中起着中心作用。嗜酸性粒细胞炎症损害上皮并导致疾病复发急性加重的机制尚未完全阐明。在本项目中，我们研究了鼻腔类固醇与转录因子在细胞内调节的有效性的分子机制。1)观察松饼窦细胞因子表达及糖皮质激素受体（GR）阳性细胞的分布。嗜酸性高的患者在松饼窦黏膜的GR β型分布密度更高。以筛窦粘膜炎性细胞浸润为主。鼻腔类固醇的使用有效地减弱了Th2细胞因子的表达。2)在体外培养的鼻窦上皮细胞中，我们检测了LPS和PGN刺激引发的转录因子NF-kB激活和伴随的细胞因子表达。结果清楚地表明，刺激后NF-kB p50活性呈剂量依赖性增加。糖皮质激素（GCs）预处理可有效抑制p50的激活。免疫细胞化学分析证实p50亚基在细胞核内易位，同时在培养细胞中糖皮质激素受体和toll样受体（TLRs） 2和4的表达。这些结果阐明了GCs和TLRs诱导的副鼻窦上皮细胞的炎症信号通路的有效抗炎作用。3)我们评估鼻窦局部滴注二丙酸倍氯米松干粉是否改善了适当手术干预后的临床和影像学状况。91.4%的患者内镜下外观评分得到改善，结果好于前一研究（71.7%）。治疗后的复仇CT评分也从5.62下降到1.93。我们认为这种新技术通过控制持续存在于窦腔内的炎症过程，对该疾病的术后治疗是有效的。少

Recent studies have implicated eosinophils as a central player in the persistent inflammation occurring in non-infectious chronic sinusitis. The mechanisms by which eosinophilic inflammation damages the epithelium and contributes to recurrent acute exacerbations in the disease have not been fully elucidated. In the present project, we have investigated molecular mechanisms of effectiveness of nasal steroids in relation to intracellular regulation by transcription factors.1) We examined cytokine expression and the distribution of glucocorticoid receptor (GR) -positive cells in the sinus muffin The patients with high eosinophilia showed higher density of GR type β distribution in the sinus mucosa. The tendency was dominant especially in infiltrating inflammatory cells in the ethmoid sinus mucosa. The use of nasal steroids effectively attenuated Th2 cytokine expression.2)We examined transcription factor NF-kB activation and concomitant cytokine expression triggered by LPS and PGN stimulus … More in cultured sinus epithelial cells. The results clearly demonstrate an increase of NF-kB p50 activity after the stimulation in a dose-dependent manner. Pretreatment with glucocorticoids (GCs) effectively inhibited the p50 activation. Immunocytochemical analysis confirmed cellular translocation of p50 subunits into the nucleus with concomitant expression of glucocorticoid receptors and toll-like receptors (TLRs) 2 and 4 in culture cells. These results elucidate the potent anti-inflammatory effects of GCs and inflammatory signal pathways induced though TLRs in paranasal sinus epithelial cells.3)We assessed whether topical instillation of beclomethasone dipropionate dry powder onto the paranasal sinus improved the clinical and radiological conditions after appropriate surgical intervention. Improvement in the endoscopic appearance scores was obtained in 91.4% of patients and the result was better than that from the previous study (71.7%). Significant decreases in the avenged CT scores were also noted from 5.62 to 1.93 after treatment. We consider that this novel technique is effective for the post-surgical treatment of the disease through the control of the inflammatory process that persists in the sinus cavity. Less