1. Effect of Cyclosporine A on Th1/Th2 Cytokine Production by Decidual Stromal Cells Mediated by Trophoblast-derived Galectin-9.
- Author
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Mei J, Wu B, Li M, Ma L, Yang X, Ma Y, and Huang Y
- Subjects
- Humans, Female, Pregnancy, Hepatitis A Virus Cellular Receptor 2 metabolism, Cell Line, Cells, Cultured, Immunosuppressive Agents pharmacology, Signal Transduction drug effects, Galectins metabolism, Trophoblasts metabolism, Trophoblasts drug effects, Cyclosporine pharmacology, Cytokines metabolism, Th1 Cells drug effects, Th1 Cells metabolism, Th1 Cells immunology, Decidua metabolism, Decidua drug effects, Decidua cytology, Th2 Cells drug effects, Th2 Cells metabolism, Th2 Cells immunology, Stromal Cells drug effects, Stromal Cells metabolism
- Abstract
This study aimed to investigate the effect of cyclosporine A (CsA) on secretion of Th1 and Th2 cytokines by decidual stromal cells (DSCs) mediated by galectin (Gal)-9.HTR8/SVneo cells and primary trophoblasts were used for in vitro studies. Gal-9 expression was measured using quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay, CsA was used to regulate Gal-9 expression in trophoblasts. DSCs were treated with trophoblast supernatant and changes in Th1 and Th2 cytokine levels were analyzed. Changes in DSC levels of the T-cell immunoglobulin mucin receptor 3 (TIM-3) levels in DSCs after treatment with Gal-9 were assessed. Western blotting and ERK and AKT inhibitors were used to assess the involvement of the corresponding signaling pathways. Gal-9 was expressed by both primary trophoblasts and HTR8/SVneo cells. CsA treatment increased Gal-9 secretion by trophoblasts, which in turn increased IL-6 (Th2 cytokine) and decreased TNF-α and IFN-γ (Th1 cytokines) secretion in DSCs. Upon downregulation of trophoblast Gal-9 secretion, DSCs secreted lower levels of Th2 cytokines and higher levels of Th1 cytokines, and the effect was reversed by addition of CsA. TIM-3 expression changed in parallel with Gal-9 secretion. CsA treatment upregulated expression of Gal-9 in trophoblasts, promoted secretion of Th2 cytokines, and inhibited secretion of Th1 cytokines via ERK signaling., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)
- Published
- 2024
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