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辛拉利醇内酯抑制脂多糖诱导的树突状细胞的表型和功能成熟。

Sinulariolide suppresses LPS‑induced phenotypic and functional maturation of dendritic cells.

机构信息

Institute of Bioinformatics and Structural Biology and Department of Medical Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan, R.O.C.

Department of Medical Research, Changhua Christian Hospital, Changhua 50006, Taiwan, R.O.C.

出版信息

Mol Med Rep. 2017 Nov;16(5):6992-7000. doi: 10.3892/mmr.2017.7480. Epub 2017 Sep 13.

Abstract

The dendritic cell (DC) maturation process is essential for the development of T cell responses and immune tolerance. Accordingly, DCs are considered a major target in the development of immunomodulating agents. In the present study, the effect of sinulariolide, an active compound isolated from the cultured soft coral Sinularia flexibilis, on lipopolysaccharide (LPS)‑induced murine bone marrow‑derived DCs was evaluated. The different phenotypes, cytokine secretion and the mix‑lymphocyte reaction of DCs were detected using flow cytometry and ELISA. The experimental results revealed that the phenotypic and functional maturation of DCs stimulated by LPS were markedly reduced by sinulariolide in a concentration‑dependent manner, including the expression of co‑stimulatory molecules (CD40, CD80 and CD86). In addition, sinulariolide reduced the release of tumor necrosis factor‑α, interleukin (IL)‑6, IL‑12 and nitric oxide from the LPS‑activated DCs, decreased their abilities to stimulate allogeneic T cell proliferation, and inhibited LPS‑induced nuclear factor‑κB pathways. These findings offer novel insight into the immunopharmacological function of sinulariolide and its effects on DCs.

摘要

树突状细胞 (DC) 的成熟过程对于 T 细胞反应和免疫耐受的发展至关重要。因此,DC 被认为是免疫调节剂开发的主要目标。在本研究中,评估了从培养的软珊瑚 Sinularia flexibilis 中分离得到的活性化合物 sinulariolide 对脂多糖 (LPS) 诱导的鼠骨髓来源的 DC 的影响。通过流式细胞术和 ELISA 检测 DC 的不同表型、细胞因子分泌和混合淋巴细胞反应。实验结果表明,sinulariolide 以浓度依赖的方式显著降低 LPS 刺激的 DC 的表型和功能成熟,包括共刺激分子 (CD40、CD80 和 CD86) 的表达。此外,sinulariolide 减少了 LPS 激活的 DC 中肿瘤坏死因子-α、白细胞介素 (IL)-6、IL-12 和一氧化氮的释放,降低了它们刺激同种异体 T 细胞增殖的能力,并抑制了 LPS 诱导的核因子-κB 途径。这些发现为 sinulariolide 的免疫药理学功能及其对 DC 的影响提供了新的见解。

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