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Tobacco Smoking Could Accentuate Epithelial-Mesenchymal Transition and Th2-Type Response in Patients With Chronic Rhinosinusitis With Nasal Polyps

  • Ki-Il Lee (Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Konyang University) ;
  • Younghwan Han (Priority Research Center, Myunggok Medical Research Institute, College of Medicine, Konyang University) ;
  • Jae-Sung Ryu (Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Konyang University) ;
  • Seung Min In (Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Konyang University) ;
  • Jong-Yeup Kim (Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Konyang University) ;
  • Joong Su Park (Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Konyang University) ;
  • Jong-Seok Kim (Myunggok Medical Research Institute, College of Medicine, Konyang University) ;
  • Juhye Kim (Department of Medicine, College of Medicine, Konyang University) ;
  • Jubin Youn (Department of Medicine, College of Medicine, Konyang University) ;
  • Seok-Rae Park (Priority Research Center, Myunggok Medical Research Institute, College of Medicine, Konyang University)
  • Received : 2021.11.10
  • Accepted : 2022.06.08
  • Published : 2022.08.31
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Abstract

Tobacco smoking (TS) has been known as one of the most potent risk factors for airway inflammatory diseases. However, there has been a paucity of information regarding the immunologic alteration mediated by TS in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). To identify the effect of TS, we harvested human tissue samples (never smoker: n=41, current smoker: n=22, quitter: n=23) and analyzed the expression of epithelial-derived cytokines (EDCs) such as IL-25, IL-33, and thymic stromal lymphopoietin. The expressions of Th2 cytokines and total serum IgE showed a type-2 inflammatory alteration by TS. In addition, the epithelial marker E-cadherin and epithelial-mesenchymal transition (EMT)-associated markers (N-cadherin, α-SMA, and vimentin) were evaluated. Histological analysis showed that EDC expressions were upregulated in the current smoker group and downregulated in the quitter group. These expression patterns were consistent with mRNA and protein expression levels. We also found that the local Th2 cytokine expression and IgE class switching, as well as serum IgE levels, were elevated in the current smoker group and showed normal levels in the quitter group. Furthermore, the expressions of E-cadherin decreased while those of N-cadherin, α-SMA, and vimentin increased in the current smoker group compared those in the never smoker group. Taken together, these results indicate that TS contributes to the deterioration of pathogenesis by releasing local EDCs and Th2 cytokines, resulting in EMT in patients with CRSwNP. We verified that alterations of immunological response by TS in sinonasal epithelium can play a vital role in leading to CRSwNP.

Keywords

Acknowledgement

This work was supported by Konyang University Myunggok Research Fund of 2019. And, this research was supported by the Priority Research Centers Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology (MEST) (NRF-2017R1A6A1A03015713).

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