γ干扰素预处理的猫脂肪组织来源间充质干细胞通过 PGE₂ 通路增强免疫调节作用。

Feline adipose tissue-derived mesenchymal stem cells pretreated with IFN-γ enhance immunomodulatory effects through the PGE₂ pathway.

机构信息

Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Science, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.

Department of Veterinary Medicine, College of Agriculture, Yanbian University, Yanji, Jilin 133000, China.

出版信息

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

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.

背景

预处理炎症刺激物用于提高来自不同物种（如鼠、人、犬）的干细胞中抗炎剂的分泌。然而，关于猫干细胞的研究很少。

目的

本研究旨在评估干扰素-γ（IFN-γ）预处理的猫脂肪组织来源（fAT）间充质干细胞（MSCs）的免疫调节能力。

方法

为了评估淋巴细胞和巨噬细胞与 IFN-γ预处理的 fAT-MSCs 的相互作用，用 IFN-γ预处理的 MSC 条件培养基培养小鼠脾细胞和 RAW 264.7 细胞。

结果

IFN-γ预处理增加了 MSC 中环氧化酶-2、吲哚胺 2,3-双加氧酶、肝细胞生长因子和转化生长因子-β 1 的基因表达水平。与未处理的 MSC 条件培养基相比，IFN-γ预处理的 MSC 条件培养基增加了 M2 巨噬细胞标志物和调节性 T 细胞标志物的表达水平。此外，前列腺素 E₂（PGE₂）抑制剂 NS-398 减弱了 MSC 的免疫调节潜能，表明 IFN-γ刺激诱导的 PGE₂水平升高是 IFN-γ预处理 MSC 免疫调节能力的关键因素。