Journal of Veterinary Science

The Korean Society of Veterinary Science (대한수의학회)
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Feline adipose tissue-derived mesenchymal stem cells pretreated with IFN-γ enhance immunomodulatory effects through the PGE2 pathway

  • Park, Seol-Gi (Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Science, College of Veterinary Medicine, Seoul National University) ;
  • An, Ju-Hyun (Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Science, College of Veterinary Medicine, Seoul National University) ;
  • Li, Qiang (Department of Veterinary Medicine, College of Agriculture, Yanbian University) ;
  • Chae, Hyung-Kyu (Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Science, College of Veterinary Medicine, Seoul National University) ;
  • Park, Su-Min (Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Science, College of Veterinary Medicine, Seoul National University) ;
  • Lee, Jeong-Hwa (Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Science, College of Veterinary Medicine, Seoul National University) ;
  • Ahn, Jin-Ok (Department of Veterinary Internal Medicine, College of Veterinary Medicine, Kangwon National University) ;
  • Song, Woo-Jin (Department of Veterinary Internal Medicine, College of Veterinary Medicine and Research Institute of Veterinary Science, Jeju National University) ;
  • Youn, Hwa-Young (Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Science, College of Veterinary Medicine, Seoul National University)
  • Received : 2020.06.05
  • Accepted : 2021.01.07
  • Published : 2021.03.31
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Abstract

Background: Preconditioning with inflammatory stimuli is used to improve the secretion of anti-inflammatory agents in stem cells from variant species such as mouse, human, and dog. However, there are only few studies on feline stem cells. Objectives: This study aimed to evaluate the immune regulatory capacity of feline adipose tissue-derived (fAT) mesenchymal stem cells (MSCs) pretreated with interferon-gamma (IFN-γ). Methods: To assess the interaction of lymphocytes and macrophages with IFN-γ-pretreated fAT-MSCs, mouse splenocytes and RAW 264.7 cells were cultured with the conditioned media from IFN-γ-pretreated MSCs. Results: Pretreatment with IFN-γ increased the gene expression levels of cyclooxygenase-2, indoleamine 2,3-dioxygenase, hepatocyte growth factor, and transforming growth factor-beta 1 in the MSCs. The conditioned media from IFN-γ-pretreated MSCs increased the expression levels of M2 macrophage markers and regulatory T-cell markers compared to those in the conditioned media from naive MSCs. Further, prostaglandin E2 (PGE2) inhibitor NS-398 attenuated the immunoregulatory potential of MSCs, suggesting that the increased PGE2 levels induced by IFN-γ stimulation is a crucial factor in the immune regulatory capacity of MSCs pretreated with IFN-γ. Conclusions: IFN-γ pretreatment improves the immune regulatory profile of fAT-MSCs mainly via the secretion of PGE2, which induces macrophage polarization and increases regulatory T-cell numbers.

Keywords

Acknowledgement

We would like to aknowledge the Research Institute for Veterinary Science and the BK21PLUS Program for Creative Veterinary Science, Seoul National University and by the Research Institute of Veterinary Science, Jeju National University. This study was also supported by the Program of National Research Foundation of Korea through the Ministry of Education.

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