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Ginsenoside F1 Attenuates Eosinophilic Inflammation in Chronic Rhinosinusitis by Promoting NK Cell Function

  • Kim, So Jeong (Department of Biomedical Sciences, University of Ulsan College of Medicine) ;
  • Lee, Jinju (Department of Biomedical Sciences, University of Ulsan College of Medicine) ;
  • Choi, Woo Sun (Department of Biomedical Sciences, University of Ulsan College of Medicine) ;
  • Kim, Hyo Jeong (Department of Biomedical Sciences, University of Ulsan College of Medicine) ;
  • Kim, Mi-Yeon (Department of Biomedical Sciences, University of Ulsan College of Medicine) ;
  • Kim, Sun Chang (Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST)) ;
  • Kim, Hun Sik (Department of Biomedical Sciences, University of Ulsan College of Medicine)
  • Received : 2020.10.28
  • Accepted : 2021.03.25
  • Published : 2021.11.15

Abstract

Background: Ginsenosides have beneficial effects on several airway inflammatory disorders primarily through glucocorticosteroid-like anti-inflammatory activity. Among inflammatory cells, eosinophils play a major pathogenic role in conferring a risk of severe refractory diseases including chronic rhinosinusitis (CRS). However, the role of ginsenosides in reducing eosinophilic inflammation and CRS pathogenesis is unexplored. Methods: We investigated the therapeutic efficacy and underlying mechanism of ginsenoside F1 (G-F1) in comparison with those of dexamethasone, a representative glucocorticosteroid, in a murine model of CRS. The effects of G-F1 or dexamethasone on sinonasal abnormalities and infiltration of eosinophils and mast cells were evaluated by histological analyses. The changes in inflammatory cytokine levels in sinonasal tissues, macrophages, and NK cells were assessed by qPCR, ELISA, and immunohistochemistry. Results: We found that G-F1 significantly attenuated eosinophilic inflammation, mast cell infiltration, epithelial hyperplasia, and mucosal thickening in the sinonasal mucosa of CRS mice. Moreover, G-F1 reduced the expression of IL-4 and IL-13, as well as hematopoietic prostaglandin D synthase required for prostaglandin D2 production. This therapeutic efficacy was associated with increased NK cell function, without suppression of macrophage inflammatory responses. In comparison, dexamethasone potently suppressed macrophage activation. NK cell depletion nullified the therapeutic effects of G-F1, but not dexamethasone, in CRS mice, supporting a causal link between G-F1 and NK cell activity. Conclusion: Our results suggest that potentiating NK cell activity, for example with G-F1, is a promising strategy for resolving eosinophilic inflammation in CRS.

Keywords

Acknowledgement

This study was supported by the Intelligent Synthetic Biology Center of the Global Frontier Project, funded by the Ministry of Education, Science, and Technology (2013-0073185); and an MRC grant (2018R1A5A2020732) and National Research Foundation (NRF) of Korea grant (2019R1A2C2006475; 2019R1C1C1009705) funded by the Korean government (MSIT).

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