Association analysis of high-mobility group box-1 protein 1 (HMGB1)/toll-like receptor (TLR) 4 with nasal interleukins in allergic rhinitis patients.
Association analysis of high-mobility group box-1 protein 1 (HMGB1)/toll-like receptor (TLR) 4 with nasal interleukins in allergic rhinitis patients.
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DOI：
10.1016/j.cyto.2019.154880
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发表时间：
2019-11
期刊：
影响因子：
3.8
通讯作者：
Xuewei Zhu;Jianan Cong;Ben Yang;Yuxin Sun
中科院分区：
文献类型：
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作者：
Xuewei Zhu;Jianan Cong;Ben Yang;Yuxin Sun
背景高迁移率族蛋白1（HMGB 1）作为炎症介质的启动剂，在变应性鼻炎（AR）患者的鼻分泌物中起重要作用。本研究旨在探讨HMGB 1及其受体Toll样受体（TLR）4与促炎性白细胞介素（IL）的关系。方法采用酶联免疫吸附试验（ELISA）检测125例AR患者和87例健康对照者鼻腔灌洗液中IL-4、IL-5、IL-13、IL-17 A、IL-10水平及血清IgE水平。采用实时定量PCR（RT-qPCR）方法检测HMGB 1、晚期糖基化终产物受体（RECEPTOR for Advanced Glycation End Products，RECEPTOR）和TLR 2、3、4的mRNA水平。采用斯皮尔曼等级相关分析任何两个因素的临床特征和实验室检查的生物标志物之间的关系。结果IL-4，-5，-13和-17 A显着高于鼻灌洗液样本中AR患者，而IL-10显着低于对照组。HMGB 1、TLR 2和TLR 4在这些AR患者的鼻腔刷拭样本中观察到高表达，而TLR 3和TLR 4的mRNA水平无显著差异。此外，HMGB 1/TLR 4 mRNA水平与IL-4、-5、-13和-17 A呈正相关，而与IL-10呈负相关。HMGB 1/TLR 4与IL-4、IL-5、IL-13、IL-17 A呈线性正相关，与IL-10呈线性负相关。结论AR患者鼻腔刷拭标本中HMGB 1、TLR 4 mRNA水平较高，与IL-4、IL-5、IL-13、IL-17 A呈正相关，与IL-10呈负相关。HMGB 1/TLR 4信号通路可能成为变应性鼻炎免疫治疗的有效靶点。
BackgroundHigh mobility group box 1 (HMGB1) acts as an inflammatory mediator initiator, and has shown to increase in nasal secretions of allergic rhinitis (AR) patients. The purpose of the present study was to investigate the association of HMGB1 and its receptor, toll-like receptor (TLR) 4 with proinflammatory interleukins in AR patients.MethodsThe interleukin (IL) −4, −5, −13, −17A, −10 in nasal lavage fluid and the serum IgE were examined with enzyme-linked immunosorbent assay (ELISA) in 125 AR patients or 87 healthy subjects (as control). The mRNA levels of HMGB1, receptor for advanced glycation end products (RAGE) and TLR 2, 3 and 4 were examined in these participants with real-time quantitative PCR (RT-qPCR) method. Spearman rank correlation was adopted to analyze the relationship between any two factors of clinical characteristics and laboratory-examined biomarkers.ResultsIL-4, −5, −13 and −17A were significantly higher, whereas IL-10 was markedly lower in the nasal lavage fluid samples from AR patients, compared with the control subjects. High expression of HMGB1, TLR2 and TLR4 were observed in the nasal brushing samples from these AR patients, whereas there was no significant difference for the mRNA levels of TLR3 and RAGE. Besides, HMGB1/TLR4 mRNA levels correlated positively with IL-4, −5, −13 and −17A, whereas negatively with IL-10. A linear regression of HMGB1/TLR4 was also found positively with IL-4, −5 (only for TLR4), −13 or −17A, whereas negatively with IL-10.ConclusionHigh mRNA levels of HMGB1 and TLR4 were found in the nasal brushing samples in AR patients, correlating positively with IL-4, −5, −13 or −17A, wheareas negatively with IL-10. HMGB1/TLR4 signaling pathway might be well responsive targets as immunotherapy for allergic rhinitis.