Sauter Alexander, Stern-Straeter Jens, Chang Ray C, Hörmann Karl, Naim Ramin
Universitäts-HNO-Klinik, Theodor-Kutzer-Ufer, D-68135 Mannheim, Germany.
Int J Mol Med. 2008 Apr;21(4):447-52.
Chronic rhinosinusitis (CRS) is one of the most common chronic diseases. The etiology and classification of CRS, with and without nasal polyps, remain unclear. Eosinophils and their products are important in the pathophysiology of allergic diseases and in host immunity to certain organisms. Interleukin 13 (IL-13) plays a pivotal role in eosinophilic inflammation. The migration of epithelial cells requires permanent re-establishment of the intercellular connection. Intercellular connections are maintained by the modulation of adherens junctions consisting of an E-cadherin/beta-catenin complex. In our study we examined the eosinophilic and non-eosinophilic paranasal mucosa obtained from two patients undergoing functional endoscopic sinus surgery. Cell cultures were incubated with human recombinant IL-13 for up to 72 h and beta-catenin concentration was determined with ELISA techniques. Furthermore, immunostaining for beta-catenin was used for the semi-quantitative description of specimens. We were able to ascertain a significant increase in beta-catenin expression in the eosinophilic paranasal cell culture after IL-13 administration compared to the non-eosinophilic culture. Immunostaining for beta-catenin was restricted to the membrane of the cells. Concerning the increased mural expression of beta-catenin, we presume that a fibrotic reaction similar to asthma and chronic obstructive pulmonary disease occurs in patients suffering from CRS. Furthermore, beta-catenin overexpression might be responsible for mucosal thickening and IL-13 seems to be an important marker in eosinophilic CRS.
慢性鼻-鼻窦炎(CRS)是最常见的慢性疾病之一。伴或不伴鼻息肉的CRS的病因及分类仍不明确。嗜酸性粒细胞及其产物在过敏性疾病的病理生理学以及宿主对某些生物体的免疫中起重要作用。白细胞介素13(IL-13)在嗜酸性粒细胞炎症中起关键作用。上皮细胞的迁移需要细胞间连接的永久重建。细胞间连接通过由E-钙黏蛋白/β-连环蛋白复合物组成的黏附连接的调节来维持。在我们的研究中,我们检查了从两名接受功能性内镜鼻窦手术的患者获取的嗜酸性和非嗜酸性鼻旁黏膜。将细胞培养物与人重组IL-13孵育长达72小时,并用酶联免疫吸附测定(ELISA)技术测定β-连环蛋白浓度。此外,β-连环蛋白的免疫染色用于标本的半定量描述。我们能够确定,与非嗜酸性培养物相比,给予IL-13后嗜酸性鼻旁细胞培养物中β-连环蛋白表达显著增加。β-连环蛋白的免疫染色仅限于细胞膜。关于β-连环蛋白壁表达增加,我们推测CRS患者会发生类似于哮喘和慢性阻塞性肺疾病的纤维化反应。此外,β-连环蛋白的过表达可能是黏膜增厚的原因,并且IL-13似乎是嗜酸性CRS的一个重要标志物。