HMGB1 and allergic rhinitis in children: preliminary results after corticosteroids or glycyrrhetic acid intranasal treatment
HMGB1 and allergic rhinitis in children: preliminary results after corticosteroids or glycyrrhetic acid intranasal treatment
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发表时间：
2012
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通讯作者：
C. Cuppari;A. Salpietro;L. Grasso;S. Manti;C. Salpietro
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作者：
C. Cuppari;A. Salpietro;L. Grasso;S. Manti;C. Salpietro
甘草甜素（GL）是甘草的主要成分，具有抗炎、抗病毒等作用，有望成为治疗变态反应的有效新药。据报道，GL直接与高迁移率族蛋白1（HMGB 1）结合，并抑制其活性。HMGB 1是一种新的促炎细胞因子，已被证明在几种疾病的发病机制中发挥作用。HMGB 1是一种普遍存在的核蛋白，在正常条件下，它位于细胞核中，在那里它组织染色质结构，DNA复制和转录。然而，已经认识到HMGB 1可以通过活化的单核细胞/巨噬细胞主动分泌到细胞外空间中，或者从坏死或受损细胞的细胞核被动释放。HMGB 1的主动分泌涉及从细胞核易位到细胞质中的分泌溶酶体，然后胞吐。在细胞外区域，HMGB 1调节几种不同的生物过程，如细胞分化、细胞迁移、转移和炎症反应。HMGB 1在几种炎性疾病中上调促炎细胞因子。本研究旨在验证GL鼻腔治疗是否可以改变过敏性鼻炎儿童鼻粘液高迁移率族蛋白1（HMGB 1）水平。在全球范围内，对35名儿童（19名男性和16名女性，中位年龄9.3±3.7岁）进行了评价，这些儿童患有过敏性鼻炎并对壁细胞单致敏。对照组包括24名健康儿童（11名男性和13名女性，中位年龄9.1±4.1岁）。过敏儿童被随机分配接受7天的鼻用GL治疗（n=12）、鼻用皮质类固醇治疗（n=12）或安慰剂治疗（n=11）。在基线（T0）、治疗7天（T1）后测量鼻粘液HMGB 1水平。在基线时，过敏性鼻炎儿童鼻粘液中的HMGB 1水平高于对照组（96.9 ± 19.3 ng/ml vs 9.27 ± 4.01 ng/ml; p < 0.001，图1）。在T1时，与安慰剂组（72.6 ± 12.7 ng/ml）相比，鼻用GL和CS治疗的儿童（分别为23.5 ± 6.3 ng/ml和28.14 ± 7.2 ng/ml）鼻粘液中的HMGB 1水平显著降低（p < 0.001），图2。此外，与安慰剂组相比，治疗组的症状评分显著降低（p < 0.001），而两个治疗组之间没有观察到显著差异。本研究提供的证据表明：1）鼻粘液HMGB 1水平可能是变应性鼻炎炎症的合适标志物; 2）GL鼻腔治疗可能具有糖皮质激素样抗炎作用。图1.变应性鼻炎儿童和对照组鼻粘液中HMGB 1水平（96.9 ± 19.3 ng/ml vs 9.27 ± 4.01 ng/ml; p < 0.001）
Glycyrrhizin (GL), a major component of licorice, could be considered as a new effective drug candidate to treatment of allergy, based on its anti-inflammatory activity anti-viral effects. It has been reported that GL binds directly to high mobility group box 1 (HMGB1), and inhibits its activities. The HMGB1 is a novel pro-inflammatory cytokine that has been shown to play a role in the pathogenesis of several diseases. HMGB1 is a ubiquitous nuclear protein which, under normal conditions, is located in the cell nucleus, where it organizes the chromatin structure, DNA replication, and transcription. However, it has been recognized that HMGB1 can be actively secreted into the extracellular space by activated monocyte/ macrophages, or passively released from the nuclei of necrotic or damaged cells. The active secretion of HMGB1 involves translocation from the nucleus to secretory lysosomes in the cytoplasm, and then exocytosis. In the extracellular area, HMGB1 regulates several different biologic processes, such as cell differentiation, cell migration, metastasis, and inflammatory responses. HMGB1 up-regulates proinflammatory cytokines in several inflammatory diseases. This study aimed at verifying whether GL nasal treatment could change nasal mucus levels of high mobility group box 1 (HMGB1) in children with allergic rhinitis. Globally, 35 children (19 males and 16 females, median age 9.3±3.7 years), with allergic rhinitis and monosensitized to parietaria, were evaluated. The control group consisted of 24 healthy children (11 males and 13 females, median age 9.1±4.1 years). Allergic children were randomly assigned to receive, for seven days, nasal GL treatment (n=12), nasal corticosteroids treatment (n=12) or placebo (n=11). Nasal mucus HMGB1 levels were measured at baseline (T0), after seven days (T1) of treatment. At baseline, HMGB1 levels in nasal mucus were higher in children with allergic rhinitis than in control group (96.9 ± 19.3 ng/ml vs 9.27 ± 4.01 ng/ml; p < 0.001, fig1). At T1, HMGB1 levels in nasal mucus were significantly diminished (p < 0.001) in children treated with nasal GL and CS (23.5 ± 6.3 ng/ml and 28.14 ± 7.2 ng/ml respectively) compared to the placebo group (72.6 ± 12.7 ng/ml), fig2. Moreover, the symptom scores were significantly decreased (p < 0.001) in children treated compared to the placebo group, whereas no significant difference was observed between the two treatment groups.The present study provides evidence that: 1) nasal mucus HMGB1 levels could be a suitable markers of inflammation in allergic rhinitis; 2) GL nasal treatment could have glucocorticoid-like anti-inflammatory effects. Fig1. HMGB1 levels in nasal mucus in children with allergic rhinitis and in control group (96.9 ± 19.3 ng/ml vs 9.27 ± 4.01 ng/ml; p < 0.001)