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荜澄茄素( Pogostemon cablin ( Blanco ) Benth )对 T 细胞的抑制作用:体外和体内免疫抑制分析。

T cell inhibition by pogostone from Pogostemon cablin (Blanco) Benth: In vitro and in vivo immunosuppressive analysis.

机构信息

State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Institute of Microbiology, Guangzhou, Guangdong 510070, P.R. China.

Cancer Research Institute, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.

出版信息

Mol Med Rep. 2017 Oct;16(4):4511-4520. doi: 10.3892/mmr.2017.7147. Epub 2017 Aug 2.

Abstract

Various plant-derived compounds exhibit immunosuppressive activity in pre‑clinical investigations, suggesting that they may serve as natural alternatives for the prevention of inflammatory disorders and autoimmune diseases. The aim of the current study was to explore the immunosuppressive potential of pogostone (PO) derived from Pogostemon cablin (Blanco) Benth. Carboxyfluorescein diacetate succinimidyl ester‑labeled cell tracking demonstrated that PO (20‑80 µM) inhibited Concanavalin A (ConA)‑stimulated lymphocyte proliferation, which was mediated by G0/G1 phase arrest and accompanied by significant decreases in the expression of CD69 (early‑stage activation marker) and CD25 (mid‑stage activation marker) in T cells, as indicated by flow cytometry analysis. Furthermore, the proliferation blocking ability of PO (5‑80 µM) was not associated with cytotoxicity in normal lymphocytes or apoptosis in ConA‑stimulated lymphocytes. The inflammatory cytokine profile determination using a cytometric beads assay revealed that PO inhibited release of anti‑inflammatory interleukin (IL)‑10 and pro‑inflammatory IL‑6 from the stimulated lymphocytes. Furthermore, PO (10, 20 or 40 mg/kg) ameliorated the T‑cell mediated delayed type hypersensitivity response in Balb/c mice by reducing leukocyte infiltration and tissue edema, providing a further validation of the direct immunosuppressive activity of PO. Together, the present data suggest that PO would suppress T cell response via a direct non‑cytotoxic inactivation at the early stage, accompanied by regulation of the inflammatory cytokine profile, which highlights clinical implications for treatment of immune-based disorders.

摘要

各种植物衍生化合物在临床前研究中表现出免疫抑制活性,这表明它们可能成为预防炎症性疾病和自身免疫性疾病的天然替代品。本研究旨在探讨来源于 Pogostemon cablin (Blanco) Benth 的 Pogostone (PO) 的免疫抑制潜力。羧基荧光素二乙酸琥珀酰亚胺酯标记的细胞示踪实验表明,PO(20-80 μM)抑制刀豆蛋白 A(ConA)刺激的淋巴细胞增殖,这是通过 G0/G1 期阻滞介导的,同时 T 细胞中 CD69(早期激活标志物)和 CD25(中期激活标志物)的表达显著下降,流式细胞术分析结果表明。此外,PO(5-80 μM)的增殖阻断能力与正常淋巴细胞的细胞毒性或 ConA 刺激的淋巴细胞凋亡无关。使用流式细胞术检测细胞因子分析发现,PO 抑制了刺激淋巴细胞中抗炎性白细胞介素(IL)-10 和促炎性 IL-6 的释放。此外,PO(10、20 或 40 mg/kg)通过减少白细胞浸润和组织水肿,改善了 Balb/c 小鼠的 T 细胞介导的迟发型超敏反应,进一步验证了 PO 的直接免疫抑制活性。综上所述,这些数据表明,PO 通过在早期阶段直接非细胞毒性失活来抑制 T 细胞反应,同时调节炎症性细胞因子谱,这突出了其在治疗免疫相关疾病方面的临床意义。

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