Characterization of IL-18 Expression and Release in the Pathogenesis of Chronic Rhinosinusitis
Characterization of IL-18 Expression and Release in the Pathogenesis of Chronic Rhinosinusitis
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DOI：
10.1159/000341668
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发表时间：
2012-10
影响因子：
2.8
通讯作者：
M. Okano;T. Fujiwara;S. Makihara;Rumi Fujiwara;T. Higaki;S. Kariya;Yohei Noda;Takenori Haruna;K. Nishizaki
中科院分区：
文献类型：
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作者：
M. Okano;T. Fujiwara;S. Makihara;Rumi Fujiwara;T. Higaki;S. Kariya;Yohei Noda;Takenori Haruna;K. Nishizaki
背景：白细胞介素-18 （IL-18）是影响慢性炎症的IL-1细胞因子家族的一员。我们试图表征IL-18的表达并研究其在慢性鼻窦炎（CRS）中的释放。方法：采用免疫组化方法检测CRS和非CRS患者鼻息肉（NPs）和钩状组织（ut）中IL-18的表达。对分散的NP细胞（DNPCs）进行不同刺激或不刺激培养后，测定培养上清液中IL-18的水平。此外，我们还研究了IL-18中和对肠毒素葡萄球菌B （SEB）诱导的细胞因子产生的影响。结果：白细胞介素-18在NPs和UTs之间的上皮层表达相似。然而，与没有CRS的ut相比，NPs的固有层中IL-18+细胞数量显著增加。增加的数量与鼻窦炎的放射学严重程度和局部嗜酸性粒细胞增多显著相关。弥散后，IL-18由NP细胞以相依赖的方式自发释放。虽然SEB、真菌抗原和TLR激动剂没有促进IL-18的释放，但暴露于蛋白酶或一个周期的冻融处理确实诱导IL-18从休息的DNPCs中释放。此外，中和IL-18可显著抑制seb诱导的IL-5、IL-13和IFN-γ，但不能抑制IL-17A的产生。结论：这些结果提示，危险信号释放的IL-18的促炎作用可能通过增加Th2-和th1相关细胞因子的产生参与了CRS的发病机制，包括嗜酸性炎症和NP的形成。
Background: Interleukin-18 (IL-18) is a member of the IL-1 cytokine family that affects chronic inflammation. We sought to characterize IL-18 expression and investigate its release during chronic rhinosinusitis (CRS). Methods: The expression of IL-18 in nasal polyps (NPs) and uncinate tissues (UTs) from both CRS and non-CRS patients was examined via immunohistochemistry. After culturing dispersed NP cells (DNPCs) with or without various stimulations, IL-18 levels were measured in the culture supernatants. Furthermore, the effect of IL-18 neutralization on staphylococcus enterotoxin B (SEB)-induced cytokine production was also examined. Results: Similar expression of IL-18 in the epithelial layers was observed between the NPs and UTs. However, there was a significantly higher number of IL-18+ cells in the lamina propria from NPs compared to UTs without CRS. This increased number was significantly correlated with the radiological severity of sinusitis and local eosinophilia. After the dispersion, IL-18 was spontaneously released by NP cells in a phase-dependent manner. While SEB, fungal antigens, and TLR agonists did not enhance the release, exposure to protease or one cycle of a freeze-and-thaw treatment did induce release of IL-18 from rested DNPCs. In addition, neutralization of IL-18 significantly suppressed SEB-induced IL-5, IL-13, and IFN-γ, but not IL-17A production. Conclusions: These results suggest that the pro-inflammatory effect of IL-18 released by danger signals may be involved in the pathogenesis of CRS, which includes eosinophilic inflammation and NP formation, via the augmentation of both Th2- and Th1-associated cytokine production.