J Vet Sci.  2021 Mar;22(2):e16. 10.4142/jvs.2021.22.e16.

Feline adipose tissue-derived mesenchymal stem cells pretreated with IFN-γ enhance immunomodulatory effects through the PGE 2 pathway

• Park SG
• An JH
• Li Q
• Chae HK
• Park SM
• Lee JH
• Ahn JO
• Song WJ
• Youn HY

• KMID: 2514461
• DOI: http://doi.org/10.4142/jvs.2021.22.e16

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 factorbeta 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 E ₂ (PGE ₂ ) inhibitor NS-398 attenuated the immunoregulatory potential of MSCs, suggesting that the increased PGE 2 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 PGE ₂ , which induces macrophage polarization and increases regulatory T-cell numbers.

Keyword

Cats; mesenchymal stem cell; macrophage; interferon-gamma; prostaglandin E ₂