基于高迁移率族蛋白B1/Toll样受体4信号途径研究慢性鼻-鼻窦炎伴鼻息肉发病过程中炎性因子的表达

Study on the expression of inflammatory factors during the pathogenesis of chronic rhinosinusitis with nasal polyps based on HMGB1/TLR4 signaling pathway

目的探讨基于高迁移率族蛋白B1(HMGB1)/Toll样受体4(TLR4)信号研究慢性鼻-鼻窦炎伴鼻息肉(chronic rhinosinusitis with nasal polyp,CRSwNP)发病过程中炎性因子的表达。方法HE检测CRSwNP中的嗜酸细胞;免疫组织化学、qRT-PCR和Western blot检测CRSwNP中HMGB1的表达;qRT-PCR检测CRSwNP中IL-4和IL-13的表达;ELISA检测HMGB1(HMGB1/TLR4通路)对人鼻黏膜上皮细胞中IL-4和IL-13表达的影响。结果CRSwNP中嗜酸细胞浸润增加(P<0.001),HMGB1表达上调(P<0.001),IL-4 mRNA和IL-13 mRNA的表达增加(P均<0.01);HMGB1使人鼻黏膜上皮细胞中IL-4和IL-13的表达增加(P均<0.001);与HMGB1(100 ng/ml)孵育组比较,加入抗TLR4抗体孵育后人鼻黏膜上皮细胞中IL-4和IL-13的表达水平降低(P均<0.001)。结论CRSwNP组织中HMGB1高表达。脂多糖刺激人鼻黏膜上皮细胞中HMGB1的产生,进而通过TLR4上调人鼻黏膜上皮细胞中IL-4和IL-13的产生。

OBJECTIVE To investigate the expression of inflammatory factors in the pathogenesis of chronic rhinosinusitis with nasal polyp(CRSwNP)based on HMGB1/TLR4 signal pathway.METHODS Eosinophils in CRSwNP were detected by HE.The expression of HMGB1 in CRSwNP was detected by immunohistochemistry,qRTPCR and Western blot.The expression of IL-4 and IL-13 in CRSwNP was detected by qRT-PCR.ELISA was used to detect the effects of HMGB1(HMGB1/TLR4 pathway)on the expression of IL-4 and IL-13 in human nasal epithelial cells.RESULTS The number of eosinophils in CRSwNP increased significantly(P<0.001),HMGB1 expression was significantly up-regulated(P<0.001),the expression levels of IL-4 mRNA and IL-13 mRNA were significantly increased(both P<0.01);HMGB1 increased the expression levels of IL-4 and IL-13 in human nasal epithelial cells(both P<0.001);Compared with HMGB1(100 ng/ml)group,the expression levels of IL-4 and IL-13 in nasal mucosal epithelial cells after 24 h of incubation with anti-TLR4-blocking antibody were significantly decreased(both P<0.001).CONCLUSION HMGB1 is highly expressed in CRSwNP tissue.LPS stimulated HMGB1 production in human nasal epithelial cells,and then up-regulated IL-4 and IL-13 production in human nasal epithelial cells through TLR4.