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Differential Hrd1 Expression and B-Cell Accumulation in Eosinophilic and Non-eosinophilic Chronic Rhinosinusitis With Nasal Polyps

  • Chen, Kun (Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine) ;
  • Han, Miaomiao (Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine) ;
  • Tang, Mengyao (Department of Plastic and Reconstructive Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine) ;
  • Xie, Yadong (Key Laboratory of Molecular Virology and Immunology, Vaccine Center, Institut Pasteur of Shanghai, Chinese Academy of Sciences) ;
  • Lai, Yuting (Department of Otolaryngology-Head and Neck Surgery, Affiliated Eye, Ear, Nose and Throat Hospital, Fudan University) ;
  • Hu, Xianting (Department of Otolaryngology-Head and Neck Surgery, Affiliated Eye, Ear, Nose and Throat Hospital, Fudan University) ;
  • Zhang, Jia (Department of Otolaryngology-Head and Neck Surgery, Affiliated Eye, Ear, Nose and Throat Hospital, Fudan University) ;
  • Yang, Jun (Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine) ;
  • Li, Huabin (Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine)
  • 투고 : 2018.05.09
  • 심사 : 2018.07.08
  • 발행 : 2018.11.01

초록

Purpose: Hrd1 has recently emerged as a critical regulator of B-cells in autoimmune diseases. However, its role in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) remains largely unexplored. This study aimed to examine Hrd1 expression and B-cell accumulation and their possible roles in CRSwNP. Methods: Quantitative real-time polymerase chain reaction, immunohistochemistry, enzyme-linked immunosorbent assay and Western blotting were used to assess gene and protein expression in nasal tissue extracts. Cells isolated from nasal tissues and peripheral blood mononuclear cells were characterized by flow cytometry. Local antibody production was measured in tissue extracts with a Bio-Plex assay. Additionally, changes in Hrd1 expression in response to specific inflammatory stimuli were measured in cultured dispersed polyp cells. Results: Nasal polyps (NPs) from patients with eosinophilic CRSwNP (ECRS) had increased levels of Hrd1, B-cells and plasma cells compared with NPs from patients with non-eosinophilic CRSwNP (non-ECRS) or other control subjects (P < 0.05). The average Hrd1 levels in B-cells in NPs from ECRS patients were significantly higher than those from non-ECRS patients and control subjects (P < 0.05). NPs also contained significantly increased levels of several antibody isotypes compared with normal controls (P < 0.05). Interestingly, Hrd1 expression in cultured polyp cells from ECRS patients, but not non-ECRS patients, was significantly increased by interleukin-$1{\beta}$, lipopolysaccharide and Poly(I:C) stimulation, and inhibited by dexamethasone treatment (P < 0.05). Conclusions: Differential Hrd1 expression and B-cell accumulation between the ECRS and non-ECRS subsets suggests that they can exhibit distinct pathogenic mechanisms and play important roles in NP.

키워드

과제정보

연구 과제 주관 기관 : National Natural Science Foundation of China

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