Chen Daishi, Mao Mingfeng, Bellussi Luisa M, Passali Desiderio, Chen Lei
Department of Otolaryngology-Head and Neck Surgery, Chinese PLA General Hospital, Beijing, China.
Int Forum Allergy Rhinol. 2014 Jun;4(6):453-62. doi: 10.1002/alr.21294. Epub 2014 Feb 6.
Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by eosinophil-dominant infiltration in Europe and the United States. However, CRSwNP in Asia has shown different immunopathologic features. High-mobility group protein box 1 (HMGB1) is a DNA-binding protein that has been suggested to be involved in various chronic inflammatory diseases. The objective of this study is to investigate whether HMGB1 is augmented in the Chinese eosinophilic CRSwNP and if non-eosinophilic CRSwNP is associated with interleukin 5 (IL-5), IL-8, and tumor necrosis factor α (TNF-α).
Nasal polyps specimens were collected from 41 patients with CRSwNP (20 eosinophilic and 21 non-eosinophilic) undergoing functional endoscopic sinus surgery (FESS). Biopsies of uncinate process, and ethmoidal mucosa from 9 non-CRS patients were used as controls by means of immunohistochemistry (IHC) staining, Western blotting, and quantitative reverse-transcription polymerase chain reaction (qRT-PCR).
HMGB1-positive expression was significantly increased in the epithelium and among the large inflammatory cells infiltration in Eos CRSwNP and non-Eos CRSwNP as compared with controls (p < 0.001). The HMGB1 protein and messenger RNA (mRNA) levels of HMGB1, IL-5, IL-8, and TNF-α were significantly higher in eosinophilic CRSwNP than those from controls and non-eosinophilic CRSwNP, but no significant differences in these markers were found between non-eosinophilic CRSwNP and controls. HMGB1 expression levels correlated significantly and positively with IL-5, IL-8, and TNF-α (rs = 0.665, 0.771, and 0.724, respectively; p < 0.001) and slightly with eosinophil infiltration (rs = 0.149; p = 0.012) and the blood eosinophils count (rs = 0.225; p = 0.001) in all samples.
Upregulation of HMGB1 could be a significant marker typically in eosinophilic CRSwNP and it may also contribute to the pathogenesis of CRSwNP along with IL-5, IL-8, and TNF-α.
在欧美地区，伴鼻息肉的慢性鼻-鼻窦炎（CRSwNP）以嗜酸性粒细胞为主的浸润为特征。然而，亚洲的CRSwNP表现出不同的免疫病理特征。高迁移率族蛋白盒1（HMGB1）是一种DNA结合蛋白，已被认为与多种慢性炎症性疾病有关。本研究的目的是调查在中国嗜酸性粒细胞性CRSwNP中HMGB1是否增加，以及非嗜酸性粒细胞性CRSwNP是否与白细胞介素5（IL-5）、IL-8和肿瘤坏死因子α（TNF-α）相关。
收集41例行功能性鼻内镜鼻窦手术（FESS）的CRSwNP患者（20例嗜酸性粒细胞性和21例非嗜酸性粒细胞性）的鼻息肉标本。采用免疫组织化学（IHC）染色、蛋白质印迹法和定量逆转录聚合酶链反应（qRT-PCR），以9例非CRS患者的钩突活检组织和筛窦黏膜作为对照。
与对照组相比，嗜酸性粒细胞性CRSwNP和非嗜酸性粒细胞性CRSwNP的上皮细胞及大量炎性细胞浸润中HMGB1阳性表达显著增加（p < 0.001）。嗜酸性粒细胞性CRSwNP中HMGB1蛋白、信使核糖核酸（mRNA）水平、IL-5、IL-8和TNF-α显著高于对照组和非嗜酸性粒细胞性CRSwNP，但非嗜酸性粒细胞性CRSwNP与对照组之间这些标志物无显著差异。在所有样本中，HMGB1表达水平与IL-5、IL-8和TNF-α显著正相关（rs分别为0.665、0.771和0.724；p < 0.001），与嗜酸性粒细胞浸润轻度相关（rs = 0.149；p = 0.012），与血液嗜酸性粒细胞计数轻度相关（rs = 0.225；p = 0.001）。
HMGB1的上调可能是嗜酸性粒细胞性CRSwNP的一个重要标志物，并且它可能与IL-5、IL-8和TNF-α一起参与CRSwNP的发病机制。
