• Journal of Veterinary Science
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• v.22 no.2
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• pp.16.1-16.13
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• 2021

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.

• Journal of Ginseng Research
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• v.46 no.1
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• pp.62-70
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• 2022

Background: Maternal Toxoplasma gondii (T. gondii) infection during pregnancy has been associated with various mental illnesses in the offspring. Ginsenoside Rh2 (GRh2) is a major bioactive compound obtained from ginseng that has an anti-T. gondii effect and attenuates microglial activation through toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway. GRh2 also alleviated tumor-associated or lipopolysaccharide-induced depression. However, the effects and potential mechanisms of GRh2 on depression-like behavior in mouse offspring caused by maternal T. gondii infection during pregnancy have not been investigated. Methods: We examined GRh2 effects on the depression-like behavior in mouse offspring, caused by maternal T. gondii infection during pregnancy, by measuring depression-like behaviors and assaying parameters at the neuronal and molecular level. Results: We showed that GRh2 significantly improved behavioral measures: sucrose consumption, forced swim time and tail suspended immobility time of their offspring. These corresponded with increased tissue concentrations of 5-hydroxytryptamine and dopamine, and attenuated indoleamine 2,3-dioxygenase or enhanced tyrosine hydroxylase expression in the prefrontal cortex. GRh2 ameliorated neuronal damage in the prefrontal cortex. Molecular docking results revealed that GRh2 binds strongly to both TLR4 and high mobility group box 1 (HMGB1). Conclusion: This study demonstrated that GRh2 ameliorated the depression-like behavior in mouse offspring of maternal T. gondii infection during pregnancy by attenuating the excessive activation of microglia and neuroinflammation through the HMGB1/TLR4/NF-κB signaling pathway. It suggests that GRh2 could be considered a potential therapy in preventing and treating psychiatric disorders in the offspring mice of mothers with prenatal exposure to T. gondii infection.

• IMMUNE NETWORK
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• v.23 no.6
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• pp.48.1-48.21
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• 2023

Mesenchymal stromal/stem cells (MSCs) possess immunoregulatory properties and their regulatory functions represent a potential therapy for acute lung injury (ALI). However, uncertainties remain with respect to defining MSCs-derived immunomodulatory pathways. Therefore, this study aimed to investigate the mechanism underlying the enhanced effect of human recombinant bone morphogenic protein-2 (rhBMP-2) primed ES-MSCs (MSC^BMP2) in promoting Tregs in ALI mice. MSC were preconditioned with 100 ng/ml rhBMP-2 for 24 h, and then administrated to mice by intravenous injection after intratracheal injection of 1 mg/kg LPS. Treating MSCs with rhBMP-2 significantly increased cellular proliferation and migration, and cytokines array reveled that cytokines release by MSC^BMP2 were associated with migration and growth. MSC^BMP2 ameliorated LPS induced lung injury and reduced myeloperoxidase activity and permeability in mice exposed to LPS. Levels of inducible nitric oxide synthase were decreased while levels of total glutathione and superoxide dismutase activity were further increased via inhibition of phosphorylated STAT1 in ALI mice treated with MSC^BMP2. MSC^BMP2 treatment increased the protein level of IDO1, indicating an increase in Treg cells, and Foxp3⁺CD25⁺ Treg of CD4⁺ cells were further increased in ALI mice treated with MSC^BMP2. In co-culture assays with MSCs and RAW264.7 cells, the protein level of IDO1 was further induced in MSC^BMP2. Additionally, cytokine release of IL-10 was enhanced while both IL-6 and TNF-α were further inhibited. In conclusion, these findings suggest that MSC^BMP2 has therapeutic potential to reduce massive inflammation of respiratory diseases by promoting Treg cells.