Increase in the Level of Proinflammatory Cytokine HMGB1 in Nasal Fluids of Patients With Rhinitis and its Sequestration by Glycyrrhizin Induces Eosinophil Cell Death.

Increase in the Level of Proinflammatory Cytokine HMGB1 in Nasal Fluids of Patients With Rhinitis and its Sequestration by Glycyrrhizin Induces Eosinophil Cell Death.
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DOI:
10.3342/ceo.2015.8.2.123
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发表时间:
2015-06
影响因子:
3
通讯作者:
Chiarugi A
Chiarugi A
中科院分区:
医学2区
文献类型:
--
作者:
Cavone L;Cuppari C;Manti S;Grasso L;Arrigo T;Calamai L;Salpietro C;Chiarugi A

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核蛋白高迁移率族蛋白盒1(HMGB1)是一种促炎介质,属于促炎介质的alarmin家族,最近已成为不同急性和慢性免疫疾病的关键参与者。一些证据表明,HMGB1是主动释放的免疫细胞或被动释放的坏死细胞外。由于HMGB1能够维持慢性炎症,我们研究了不同形式鼻炎患者的鼻液中是否存在这种蛋白质。在健康受试者或接受或未接受不同治疗的鼻炎患者的鼻液中评估HMGB1水平。我们报告了过敏性鼻炎患者、NARES(非过敏性鼻炎伴嗜酸性粒细胞增多综合征)患者以及息肉患者的鼻液中HMGB1水平显著升高。我们还发现,含有HMGB1结合化合物白蛋白(GLT)的制剂降低鼻炎患者鼻液中HMGB1含量的程度与鼻用布地奈德治疗相似。我们还发现,在培养的人类白细胞群体中,嗜酸性粒细胞释放更高量的HMGB1。基于HMGB1维持嗜酸性粒细胞存活的能力和GLT抑制HMGB1的能力,我们报告GLT选择性地杀死培养的嗜酸性粒细胞,而对中性粒细胞、巨噬细胞和淋巴细胞没有影响。总的来说,这些数据强调了HMGB1在鼻炎发病机制中的作用和GLT制剂在治疗鼻粘膜慢性炎症性疾病中的治疗潜力。
The nuclear protein high mobility group protein box 1 (HMGB1) is a proinflammatory mediator that belongs to the alarmin family of proinflammatory mediators, and it has recently emerged as a key player in different acute and chronic immune disorders. Several lines of evidence demonstrate that HMGB1 is actively released extracellularly from immune cells or passively released from necrotic cells. Because of the ability of HMGB1 to sustain chronic inflammation, we investigated whether the protein is present in nasal fluids of patients with different forms of rhinitis. HMGB1 levels were evaluated in nasal fluids of healthy subjects or rhinitis patients who were treated or not treated with different treatments. We report that the level of HMGB1 was significantly increased in nasal fluids of patients with allergic rhinitis, patients with NARES (nonallergic rhinitis with eosinophiliac syndrome), as well as patients with polyps. We also found that a formulation containing the HMGB1-binding compound glycyrrhizin (GLT) reduced the HMGB1 content in nasal fluids of rhinitis patients to an extent similar to that with nasal budesonide treatment. We also found that among the cultured human leukocyte populations, eosinophils released higher amounts of HMGB1. Based on the ability of HMGB1 to sustain eosinophil survival and the ability of GLT to inactivate HMGB1, we report that GLT selectively killed cultured eosinophils and had no effect on neutrophils, macrophages, and lymphocytes. Collectively, these data underscore the role of HMGB1 in rhinitis pathogenesis and the therapeutic potential of GLT formulations in treatment of chronic inflammatory disorders of the nasal mucosa.
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