Pathophysiology of nasal polyposis: The role of desmosomal junctions
Pathophysiology of nasal polyposis: The role of desmosomal junctions
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DOI：
10.2500/ajr.2008.22.3235
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发表时间：
2008-11-01
期刊：
影响因子：
--
通讯作者：
Parkos, Charles A.
中科院分区：
文献类型：
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作者：
Zuckerman, Jodi D.;Lee, Winston Y.;Parkos, Charles A.
背景：粘膜炎症与上皮细胞间连接和屏障功能的改变有关；然而，关于细胞间连接在上呼吸道炎症性疾病中的作用知之甚少。在这项研究中，我们检测了鼻息肉细胞间连接和蛋白表达的改变。方法：术中对11例患者和6例对照组的鼻息肉和正常组织进行活检。用免疫荧光法分析组织细胞间连接蛋白的表达。同时，用肿瘤坏死因子(TNF) α、干扰素(IFN) γ和IL-13处理培养的人支气管上皮（HBE）细胞，模拟炎症条件，然后通过免疫荧光和Western blot评估连接蛋白的变化。在所分析的细胞间连接蛋白中，包括包含战斗和粘附连接的蛋白，与正常对照相比，观察到的唯一变化是鼻息肉上皮的桥粒蛋白。具体而言，与对照组相比，息肉组织中连接粒蛋白DSG(2)和DSG(3)的表达显著降低(分别为0.53 pixel/mu m(2)和1.09 pixel/mu m(2) [p = 0.009], 0.29 pixel/mu m（2)和1.11 pixel/mu m(2) [p = 0.0078]）。在体外实验中，通过免疫荧光和Western blotting分析，将培养的HBE细胞暴露于炎性细胞因子中，发现tnf - α处理导致DSG内化并降低表达(2)。用ifn - γ治疗导致DSG表达增加(2)，Western blot结果显示蛋白被切割。IL-13暴露导致DSG(2)表达下调和蛋白切割的证据。结论：鼻息肉组织中桥粒连接处DSG(2)和DSG(3)表达水平降低。这可能与粘膜炎症反应有关。暴露于Th1/Th2细胞因子的呼吸细胞系在DSG中导致类似的表达改变(2)，提示蛋白质内化和分裂。我们推测，炎症细胞因子继发于鼻黏膜的桥粒连接减弱可能有助于鼻息肉病的形成。
Background: Molly mucosal inflammatory conditions are associated with alterations in epithelial intercellular junctions and barrier function; however, little is known about the role of intercellular junctions in inflammatory diseases of the upper airways. In this study, We examined nasal polyps for altered intercellular junctions and protein expression.Methods: Biopsy specimens of nasal polyps and normal tissue were obtained intraoperatively from 11 patients and 6 controls. Tissue was analyzed for expression of intercellular junctional proteins by immunofluorescence. In parallel, cultured human bronchial epithelial (HBE) cells were treated with tumor necrosis factor (TNF) alpha, interferon (IFN) gamma, and IL-13 to simulate inflammatory conditions followed by assessment for changes in junctional proteins by immunofluorescence and Western blot,Results: Of the intercellular junctional proteins analyzed, including proteins comprising fight and adherens junctions, the only alterations observed were in desmosomal proteins in nasal polyp epithelium compared With normal controls. Specifically, expression of desmosomal proteins DSG(2) and DSG(3) were significantly decreased in polyps versus controls (0.53 pixel/mu m(2) versus 1.09 pixel/mu m(2) [p = 0.009], and 0.29 pixel/mu m(2) versus 1.11 pixel/mu m(2) [P = 0.0078], respectively). In vitro experiments involving exposure of cultured HBE cells with inflammatory cytokines revealed that TNF-alpha treatment resulted in internalization and decreased expression of DSG(2) by immunofluorescence and Western blotting. Treatment With IFN-gamma results in increased expression of DSG(2) and evidence ofprotein cleavage by Western blot. IL-13 exposure resulted in down-regulation of DSG(2) expression and evidence of protein cleavage.Conclusion: These results indicate that nasal polyps express decreased levels of DSG(2) and DSG(3) components of desmosomal junctions. This is likely linked to the mucosal inflammatory response. Exposure of a respiratory cell line to Th1/Th2 cytokines results in similar expressional alterations in DSG(2), suggesting protein internalization and cleavage. We speculate that weakened desmosomal junctions in nasal mucosa secondary to inflammatory cytokines may contribute to the formation of nasal polyposis,