白细胞介素-17A在慢性鼻窦炎发病机制中的作用研究

Role of IL-17A in the pathogenesis of chronic rhinosinusitis

目的探讨白细胞介素17A(IL-17A)在慢性鼻窦炎发病机制中的作用。方法收集38例慢性鼻窦炎伴鼻息肉(CRSwNP)患者的息肉组织、15例慢性鼻窦炎不伴鼻息肉(CRSsNP)患者的钩突组织和17例对照组黏膜组织;酶联免疫吸附实验检测组织重塑相关因子基质金属蛋白酶(MMP-2、MMP-9、TIMP-1)、IL-17A、中性粒细胞相关趋化因子(CXCL1、CXCL2、CXCL8)的蛋白水平;用免疫荧光技术检测IL-17A受体的定位情况;不同浓度IL-17A刺激游离鼻息肉细胞后,实时荧光定量PCR检测MMP-2、MMP-9、TIMP-1、CXCL1、CXCL2、CXCL8的mRNA水平。结果与对照组相比,CRSwNP组和CRSsNP组中MMP-9、IL-17A、CXCL1、CXCL2、CXCL8的表达水平均升高,CRSwNP组更明显(P<0.05)。免疫荧光显示鼻息肉组织中IL-17A受体表达于中性粒细胞;在IL-17A刺激下,游离鼻息肉细胞分泌MMP-9、CXCL1、CXCL2、CXCL8水平升高(P<0.05)。结论在慢性鼻窦炎尤其是CRSwNP中,存在显著的IL-17A高表达、中性粒细胞浸润及组织重塑水平。IL-17A促进趋化因子CXCL1、CXCL2、CXCL8的分泌诱导中性粒细胞浸润,并诱导MMP-9的产生促进炎性部位组织重塑。

Objective To explore the role of interleukin-17A(IL-17A)in the pathogenesis of chronic rhinosinusitis(CRS).Methods Nasal polyp specimens were obtained from 38 patients suffering from CRS with nasal polyps(CRSwNP),uncinate process tissues from 15 patients suffering from CRS without nasal polyps(CRSsNP),and normal mucosal tissues from 17 healthy control subjects.Enzyme-linked immunosorbent assay was used to detect the levels of IL-17A,neutrophil-associated chemokines(CXCL1,CXCL2,CXCL8)and tissue remodelling-associated factors(MMP-2,MMP-9,TIMP-1).The localization of IL-17A receptor was detected by immunofluorescence.After stimulation of dispersed nasal polyps cells(DNPCs)with different concentrations of IL-17A,mRNA levels of MMP-2,MMP-9,TIMP-1,CXCL1,CXCL2 and CXCL8 were measured by real-time fluorescence quantitative polymerase chain reaction.Results Compared with the control group,the expression levels of IL-17A,CXCL1,CXCL2,CXCL8,and MMP-9 were elevated in both the CRSwNP and CRSsNP groups,and were more significant in the CRSwNP group(P<0.05).Immunofluorescence revealed that IL-17A receptor was expressed on neutrophils in nasal polyps.The releases of CXCL1,CXCL2,CXCL8,and MMP-9 increased in DNPCs in response to IL-17A stimulation(P<0.05).Conclusions There are significant IL-17A high expression,neutrophil infiltration and tissue remodeling in CRS,especially CRSwNP.IL-17A can stimulate the releases of chemokines CXCL1,CXCL2,and CXCL8 to cause neutrophil infiltration,as well as the production of MMP-9 to promote tissue remodeling in inflammatory regions.