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西他列汀和维生素 D3 可抑制 2 型糖尿病患者辅助性 T 细胞的增殖和炎症反应。

The increased T helper cells proliferation and inflammatory responses in patients with type 2 diabetes mellitus is suppressed by sitagliptin and vitamin D3 in vitro.

机构信息

Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

Department of Internal Medicine, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

出版信息

Inflamm Res. 2019 Oct;68(10):857-866. doi: 10.1007/s00011-019-01265-5. Epub 2019 Jun 25.

Abstract

OBJECTIVE

The probably effects of sitagliptin and vitamin D3 (VitD3) on proliferation capacity and cytokines production were investigated in type 2 diabetes mellitus (T2DM) in vitro.

MATERIALS AND METHODS

Peripheral blood mononuclear cells (PBMCs) were isolated from 35 patients with T2DM and 26 healthy controls (HCs). CFSE-labeled PBMCs stimulated with phytohamagglutinin (PHA, 5 μg/mL) in the presence/absence of sitagliptin (200 mg/mL) with/without VitD3 (10 M) for 4 days. The proliferation of CD4 T helper cells and non-CD4 cells was analyzed using flow cytometry. The supernatant levels of IFN-γ, IL-17, IL-4, TGB-β and IL-37 were detected using ELISA.

RESULTS

The proliferation of CD4 T cells in response to PHA was higher in T2DM patients compared with HCs. The production of IFN-γ and IL-17 in PHA-stimulated cultures was higher, and the levels of IL-4 and IL-37 were lower in T2DM patients compared to HCs. The addition of sitagliptin or VitD3 to the cultures decreased the CD4 T cells and non-CD4 cells proliferation in patients and HCs. Sitagliptin with VitD3 was more effective in suppression of proliferation, decreasing of IL-17 and enhancing of IL-37 production.

CONCLUSION

Sitagliptin plus VitD3 effectively reduces the proliferative T cells response and modulates pro-inflammatory/anti-inflammatory cytokines production.

摘要

目的

研究西他列汀和维生素 D3(VitD3)对 2 型糖尿病(T2DM)患者体外增殖能力和细胞因子产生的可能影响。

材料与方法

从 35 例 T2DM 患者和 26 例健康对照者(HCs)中分离外周血单个核细胞(PBMCs)。用植物血凝素(PHA,5μg/mL)刺激 CFSE 标记的 PBMCs,在存在/不存在西他列汀(200mg/mL)和/或 VitD3(10M)的情况下培养 4 天。用流式细胞术分析 CD4 T 辅助细胞和非 CD4 细胞的增殖。用 ELISA 检测上清液中 IFN-γ、IL-17、IL-4、TGB-β 和 IL-37 的水平。

结果

与 HCs 相比,T2DM 患者对 PHA 的 CD4 T 细胞增殖反应更高。PHA 刺激培养物中 IFN-γ 和 IL-17 的产生更高,而 IL-4 和 IL-37 的水平更低。在培养物中添加西他列汀或 VitD3 可降低患者和 HCs 中 CD4 T 细胞和非 CD4 细胞的增殖。西他列汀加 VitD3 更有效地抑制增殖,降低 IL-17 并增强 IL-37 的产生。

结论

西他列汀加 VitD3 可有效降低增殖性 T 细胞反应,并调节促炎/抗炎细胞因子的产生。

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