The role of high-mobility group box-1 (HMGB1) in the pathogenesis of asthma
The role of high-mobility group box-1 (HMGB1) in the pathogenesis of asthma
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DOI：
10.1111/j.1365-2222.2012.03998.x
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发表时间：
2012-06-01
影响因子：
6.1
通讯作者：
Park, H. -W.
中科院分区：
文献类型：
--
作者：
Shim, E. -J.;Chun, E.;Park, H. -W.
背景高迁移率族蛋白B1（HMGB 1）是一种内源性危险信号，可抑制嗜酸性粒细胞（EOS）的存活，并作为一种趋化因子发挥作用目的探讨HMGB 1在以嗜酸性粒细胞气道炎症为特征的哮喘发病中的作用。随后使用抗HMGB 1抗体评价HMGB 1在哮喘小鼠模型中的作用。结果哮喘患者痰液中HMGB 1的表达明显高于正常对照组，且与痰液嗜酸性粒细胞增多、痰液TNF-α、IL-5和IL-13的表达呈正相关。在小鼠哮喘模型中，HMGB 1在肺组织中的表达和支气管肺泡灌洗液中的HMGB 1水平显著升高，并且通过阻断HMGB 1活性来减轻嗜酸性粒细胞气道炎症、非特异性气道高反应性和病理改变。此外，我们发现，增强的CD 11b-CD 11 c（+）表达也显着降低时，HMGB 1活性被blocked.Conclusion和临床相关性我们的研究结果表明，HMGB 1起着关键作用，在临床和实验性哮喘的特点是嗜酸性粒细胞性气道炎症的发病机制。
Background High-mobility group box 1 protein (HMGB1) belonging to endogenous danger signals prolongs eosinophil survival and acts as a chemoattractant.Objective The authors evaluated the role of HMGB1 in the pathogenesis of asthma characterized by eosinophilic airway inflammation.Methods Firstly, HMGB1 expressions in induced sputum obtained from human asthmatics were determined. This was followed by an evaluation of the role of HMGB1 in a murine model of asthma using anti-HMGB1 antibodies. Then the effect of HMGB1 on the receptor of advanced glycation end products (RAGE) expressions on CD11b-CD11c(+) cells isolated from a murine model of asthma were measured to elucidate the mechanisms involved.Results Sputum HMGB1 expressions were markedly higher in asthmatics than in normal controls, and were positively correlated with sputum eosinophilia and sputum TNF-alpha, IL-5 and IL-13 expressions. In a murine model of asthma, HMGB1 expressions in lung tissue and HMGB1 levels in bronchoalveolar lavage fluid were significantly elevated and eosinophilic airway inflammation, non-specific airway hyperresponsiveness, and pathological changes were attenuated by blocking HMGB1 activity. Furthermore, we found that enhanced RAGE expressions on CD11b-CD11c(+) also significantly decreased when HMGB1 activity was blocked.Conclusion and Clinical Relevance Our findings suggest that HMGB1 plays a key role in the pathogenesis of clinical and experimental asthma characterized by eosinophilic airway inflammation.