Feline adipose tissue-derived mesenchymal stem cells pretreated with IFN-γ enhance immunomodulatory effects through the PGE 2 pathway
- Author:
Seol-Gi PARK
1
;
Ju-Hyun AN
;
Qiang LI
;
Hyung-Kyu CHAE
;
Su-Min PARK
;
Jeong-Hwa LEE
;
Jin-Ok AHN
;
Woo-Jin SONG
;
Hwa-Young YOUN
Author Information
- Publication Type:Original Article
- From:Journal of Veterinary Science 2021;22(2):e16-
- CountryRepublic of Korea
- Language:English
-
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.