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重要作用。嗜酸性粒细胞性炎症损伤上皮细胞并导致疾病反复急性加重的机制尚未完全阐明。本课题研究了鼻用类固醇激素与转录因子细胞内调控的分子机制。1）检测了鼻窦黏膜中细胞因子的表达和糖皮质激素受体（GR）阳性细胞的分布。尤其是筛窦粘膜中的炎性细胞浸润更明显。鼻用类固醇的使用有效地减弱了Th 2细胞因子的表达。2）我们检测了LPS和PGN刺激引发的转录因子NF-κ B活化和伴随的细胞因子表达 ...更多信息 在培养的窦上皮细胞中。结果清楚地表明，刺激后NF-κ B p50活性以剂量依赖性方式增加。用糖皮质激素（GC）预处理可有效抑制p50激活。免疫细胞化学分析证实细胞易位的p50亚单位进入细胞核与糖皮质激素受体和Toll样受体（TLR）2和4在培养细胞中的伴随表达。这些结果阐明了GC的强效抗炎作用和通过TLR在鼻窦上皮细胞中诱导的炎症信号通路。3）我们评估了在适当的手术干预后，将二丙酸倍氯米松干粉局部滴注到鼻窦上是否改善了临床和放射学状况。91.4%的患者内镜外观评分改善，结果优于既往研究（71.7%）。治疗后，还观察到复仇CT评分从5.62显著降低至1.93。我们认为，这种新的技术是有效的手术后治疗的疾病，通过控制炎症过程中持续存在的窦腔。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