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Cytokine Inductions and Intracellular Signal Profiles by Stimulation of dsRNA and SEB in the Macrophages and Epithelial Cells

  • Jun-Pyo Choi (Department of Internal Medicine, Seoul National University Bundang Hospital) ;
  • Purevsuren Losol (Department of Internal Medicine, Seoul National University Bundang Hospital) ;
  • Ghazal Ayoub (S-Alpha Therapeutics, Inc.) ;
  • Mihong Ji (Department of Internal Medicine, Seoul National University Bundang Hospital) ;
  • Sae-Hoon Kim (Department of Internal Medicine, Seoul National University Bundang Hospital) ;
  • Sang-Heon Cho (Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center) ;
  • Yoon-Seok Chang (Department of Internal Medicine, Seoul National University Bundang Hospital)
  • Received : 2021.07.18
  • Accepted : 2022.03.30
  • Published : 2022.04.30
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Abstract

Foreign molecules, including viruses and bacteria-derived toxins, can also induce airway inflammation. However, to the best of our knowledge, the roles of these molecules in the development of airway inflammation have not been fully elucidated. Herein, we investigated the precise role and synergistic effect of virus-mimicking double-stranded RNA (dsRNA) and staphylococcal enterotoxin B (SEB) in macrophages and epithelial cells. To identify cytokine expression profiles, both the THP-1-derived macrophages and BEAS-2B epithelial cells were stimulated with dsRNA or SEB. A total of 21 cytokines were evaluated in the culture supernatants. We observed that stimulation with dsRNA induced cytokine production in both cell types. However, cytokine production was not induced in SEB-stimulated epithelial cells, compared to the macrophages. The synergistic effect of dsRNA and SEB was evaluated observing cytokine level and intracellular phospho-signaling. Fifteen different types were detected in high-dose dsRNA-stimulated epithelial cells, and 12 distinct types were detected in macrophages; those found in macrophages lacked interferon production compared to the epithelial cells. Notably, a synergistic effect of cytokine induction by co-stimulation of dsRNA and SEB was observed mainly in epithelial cells, via activation of most intracellular phosphor-signaling. However, macrophages only showed an accumulative effect. This study showed that the type and severity of cytokine productions from the epithelium or macrophages could be affected by different intensities and a combination of dsRNA and SEB. Further studies with this approach may improve our understanding of the development and exacerbation of airway inflammation and asthma.

Keywords

Acknowledgement

This study was supported by the grant (No. 02-2015-011) from Seoul National University Bundang Hospital (SNUBH) Research Fund and the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2020R1F1A1070600). We also express our sincere gratitude to Amb. Hong-choo Hyun and his wife for their kind donation.

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