IL-22/IL-22R1 signaling regulates the pathophysiology of chronic rhinosinusitis with nasal polyps via alteration of MUC1 expression.
IL-22/IL-22R1 signaling regulates the pathophysiology of chronic rhinosinusitis with nasal polyps via alteration of MUC1 expression.
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DOI：
10.1016/j.alit.2016.04.017
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Yasuyuki Noyama;M. Okano;T. Fujiwara;S. Kariya;T. Higaki;Takenori Haruna;S. Makihara;Kengo Kanai;Takahisa Koyama;M. Taniguchi;J. Ishitoya;A. Kanda;Yoshiki Kobayashi;M. Asako;K. Tomoda;K. Nishizaki
中科院分区：
文献类型：
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作者：
Yasuyuki Noyama;M. Okano;T. Fujiwara;S. Kariya;T. Higaki;Takenori Haruna;S. Makihara;Kengo Kanai;Takahisa Koyama;M. Taniguchi;J. Ishitoya;A. Kanda;Yoshiki Kobayashi;M. Asako;K. Tomoda;K. Nishizaki
背景：IL-22是IL-10家族细胞因子，调节慢性炎症。方法：采用免疫组化和实时荧光定量PCR方法检测慢性鼻窦炎伴鼻息肉（CRS）患者鼻息肉和钩突组织中IL-22和IL-22 R1蛋白和mRNA的表达，并与正常对照组比较。将分散的NP和UT细胞与金黄色葡萄球菌外毒素、葡萄球菌肠毒素B和α-毒素一起培养，随后分析外毒素诱导的IL-22水平及其与临床病理因素的关联。结果：NP中IL-22和IL-22 R1分别主要表达在浸润的炎症细胞和上皮细胞中。NP中的IL-22 mRNA水平显着高于非CRS患者的UT，而NP中的IL-22 R1水平相反较低。NP细胞产生大量的IL-22响应外毒素。外毒素诱导的NP细胞产生IL-22与局部嗜酸性粒细胞增多的程度和术后计算机断层扫描（CT）评分显著负相关，而相反，它与第一秒用力呼气量（FEV 1）/用力肺活量（FVC）比值呈正相关。IL-22显著增强NP细胞MUC 1 mRNA的表达。在NP中，IL-22诱导的MUC 1 mRNA水平与IL-22 R1 mRNA水平显著正相关。结论：这些数据表明，IL-22/IL-22 R1信号转导的不平衡通过MUC 1表达的改变调节CRSwNP的发病机制，包括局部嗜酸性粒细胞增多。
Background: IL-22 is an IL-10-family cytokine that regulates chronic inflammation. We investigated the role of IL-22 and its receptor, IL-22R1, in the pathophysiology of chronic rhinosinusitis with nasal polyps (CRSwNP).Methods: IL-22 and IL-22R1 protein and mRNA expression in NP and in uncinate tissues (UT) from CRS and non-CRS patients was examined using immunohistochemistry and real-time PCR, respectively. Dispersed NP and UT cells were cultured with the Staphylococcus aureus exotoxins, staphylococcal enterotoxin B and alpha-toxin, following which exotoxin-induced IL-22 levels and their association with clinicopathological factors were analyzed. Effects of IL-22 on MUC1 expression and cytokine release in NP cells were also determined.Results: IL-22 and IL-22R1 in NP were mainly expressed in infiltrating inflammatory cells and in epithelial cells, respectively. IL-22 mRNA levels in NP were significantly higher than those in UTs from non-CRS patients whereas IL-22R1 levels were conversely lower in NPs. NP cells produced substantial amounts of IL-22 in response to exotoxins. Exotoxin-induced IL-22 production by NP cells significantly and negatively correlated with the degree of local eosinophilia and postoperative computed tomography (CT) score, whereas conversely it positively correlated with the forced expiratory volume in 1s (FEV1)/forced vital capacity (FVC) ratio. IL-22 significantly enhanced MUC1 mRNA expression in NP cells. IL-22-induced MUC1 mRNA levels were significantly and positively correlated with IL-22R1 mRNA levels in NPs. Conclusions: These data suggest that imbalance of IL-22/IL-22R1 signaling regulates the pathogenesis of CRSwNP, including local eosinophilia, via alteration of MUC1 expression.