白细胞介素-33 通过 NF-κB 信号通路促进鼻息肉慢性鼻窦炎的炎症反应。

Interleukin-33 promotes the inflammatory reaction in chronic rhinosinusitis with nasal polyps by NF-κB signaling pathway.

机构信息

Department of Otorhinolaryngology-Head and Neck Surgery, Shengjing Hospital, China Medical University, Shenyang Shi, Liaoning Sheng, China.

出版信息

Eur Rev Med Pharmacol Sci. 2017 Oct;21(20):4501-4508.

PMID:29131267

Abstract

OBJECTIVE

Interleukin (IL)-33 promotes T helper (Th2) immune response and may be involved in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). Using murine and human specimens, we evaluated the role of IL-33 in CRSwNP.

MATERIALS AND METHODS

To establish CRSwNP, Balb/c mice were sensitized with house dust mite, followed up by intranasal exposure to Staphylococcus aureus to stimulate the inflammatory response of nasal mucosa. The hematoxylin-eosin staining and total serum IgE were used to the successful construction of CRSwNP model. For mechanistic studies, we blocked mice with IL-33 and the Th2 cells counts in tissue were detected. Th2 cytokine expression of IL-4, IL-5, IL-13, IL-22, CCL-11, and CCL-24 in control group, CRSwNP group and IL-33 blockade group at 12 weeks after CRSwNP model establishment, were analyzed by qRT-PCR. Meanwhile, the relative mRNA and protein expression levels of NF-κB, MyD88 and TLR7 were detected after IL-33 blockade. To document the inflammatory response in patients with CRSwNP, The relative mRNA expression of IL-4, IL-5, IL-13, IL-22, CCL-11, and CCL-24 in control individuals and patients with CRSwNP (chronic rhinosinusitis with nasal polyps) were analyzed by qRT-PCR.

RESULTS

The CRSwNP model was successfully constructed. After IL-33 blocked, the relative expression of IL-33 and Th2 cells counts were reduced significantly. CRSwNP mice showed overproduction of IL-4, IL-5, IL-13, IL-22, CCL-11, and CCL-24 and IL-33 blockade inhibited the expression of IL-4, IL-5, IL-13, IL-22, CCL-11, and CCL-24. Furthermore, IL-33 blockade decreased the mRNA levels of NF-κB, MyD88 and TLR7, and also restrained the protein expression of them. On the other hand, patients' specimens with CRSwNP showed high levels of Th2 cytokines including IL-33, IL-4, IL-5, IL-13, IL-22, CCL-11, and CCL-24.

CONCLUSIONS

CRSwNP is associated with overexpression of IL-33, with subsequent activation of Th2 immune response by NF-κB signaling pathway.

摘要

目的

白细胞介素（IL）-33 可促进辅助性 T 细胞（Th2）免疫应答，可能参与慢性鼻-鼻窦炎伴鼻息肉（CRSwNP）的发病机制。本研究使用鼠类和人类标本评估了 IL-33 在 CRSwNP 中的作用。

材料和方法

为建立 CRSwNP 模型，将 Balb/c 小鼠用屋尘螨致敏，然后用金黄色葡萄球菌滴鼻以刺激鼻黏膜的炎症反应。通过苏木精-伊红染色和总血清 IgE 评估 CRSwNP 模型的成功构建。为进行机制研究，用 IL-33 阻断剂对小鼠进行阻断，并检测组织中的 Th2 细胞计数。在建立 CRSwNP 模型 12 周后，通过 qRT-PCR 分析对照组、CRSwNP 组和 IL-33 阻断组中 IL-4、IL-5、IL-13、IL-22、CCL-11 和 CCL-24 的 Th2 细胞因子表达。同时，检测 IL-33 阻断后 NF-κB、MyD88 和 TLR7 的相对 mRNA 和蛋白表达水平。为记录 CRSwNP 患者的炎症反应，通过 qRT-PCR 分析对照组和 CRSwNP 患者（慢性鼻-鼻窦炎伴鼻息肉）中 IL-4、IL-5、IL-13、IL-22、CCL-11 和 CCL-24 的相对 mRNA 表达水平。

结果

成功构建了 CRSwNP 模型。阻断 IL-33 后，IL-33 和 Th2 细胞计数的相对表达显著降低。CRSwNP 小鼠表现出 IL-4、IL-5、IL-13、IL-22、CCL-11 和 CCL-24 的过度产生，而 IL-33 阻断抑制了 IL-4、IL-5、IL-13、IL-22、CCL-11 和 CCL-24 的表达。此外，IL-33 阻断降低了 NF-κB、MyD88 和 TLR7 的 mRNA 水平，并抑制了它们的蛋白表达。另一方面，CRSwNP 患者的标本显示出高水平的 Th2 细胞因子，包括 IL-33、IL-4、IL-5、IL-13、IL-22、CCL-11 和 CCL-24。