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

糖皮质激素对嗜酸粒细胞性鼻窦炎影响的分子分析，参考炎症转录因子的调节。

基本信息

批准号：
18591868
负责人：
TAKENO Sachio
金额：
$ 1.95万
依托单位：
Hiroshima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

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

最近的研究已经在非感染性慢性鼻窦炎中实施了嗜酸性影响作为持续感染的核心角色。嗜酸性粒细胞影响会损害上皮的机制，并导致疾病中复发性急性加重，尚未完全阐明。 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 shown higher density of GR type β distribution in the sinus mucosa.这种趋势尤其是在淋巴结鼻窦粘膜中浸润炎症细胞的主导性。鼻固醇的使用有效地减弱了Th2细胞因子的表达。2）我们检查了转录因子NF-KB激活和与LPS和PGN刺激触发的伴有细胞因子表达……在培养的鼻窦上皮细胞中更多。结果清楚地表明，以剂量依赖性方式刺激后NF-KB P50活性的增加。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，培养细胞中p50亚基与糖皮质激素受体的表达和糖皮质激素受体（TLRS）2和4的细胞易位。这些结果阐明了GCS和炎症信号途径在副鼻窦上皮细胞中诱导的TLR的潜在抗炎作用。3）我们评估了在适当的术后局部和放射性介入后，局部插入局部刺激性倍倍氨酸磷酸二倍型二倍型二倍型干粉。 91.4％的患者获得了内窥镜外观评分的改善，结果比以前的研究更好（71.7％）。在治疗后，报仇CT评分的显着下降从5.62到1.93。我们认为，通过控制鼻腔腔中持续存在的炎症过程，这种新型技术对疾病的手术后治疗有效。较少的