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斑蝥素调节人单核细胞来源的树突状细胞的发育。

Cantharidin modulates development of human monocyte-derived dendritic cells.

机构信息

Department of Radiation Oncology, Far Eastern Memorial Hospital, Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.

出版信息

Toxicol In Vitro. 2011 Dec;25(8):1740-7. doi: 10.1016/j.tiv.2011.09.001. Epub 2011 Sep 10.

Abstract

Cantharidin (CTD), a naturally occurring small molecule isolated from a medicinal insect, possesses anti-cancer and pro-inflammatory properties. We aimed to examine the effect of CTD on human myeloid dendritic cells (DCs) by examining immature DCs differentiated and maturated from CD14+ monocytes. CTD added into a culture of starting CD14+ monocytes markedly and dose-dependently reduced viability of harvested DC. Mature DCs differentiated in the presence of CTD had much fewer, shorter membranous projections than those without CTD. Changes in morphological features characteristic of necrotic cells were also evident. Furthermore, CTD affected DC differentiation and maturation phenotypes including down-regulation of surface CD1a, CD83 and DC-SIGN. DCs derived in the presence of CTD possessed an impaired allostimulatory activity on naive CD4+CD45+RA+T cell in terms of proliferation and interferon-γ production. It suggests that CTD may redirect DC differentiation toward a less mature stage and that this effect is not solely due to its cytotoxicity. Whether this effect refers to immune suppression or tolerance to disease treatments with unwanted immune reactions needs further evaluation.

摘要

斑蝥素(CTD)是一种从药用昆虫中分离出来的天然小分子,具有抗癌和促炎作用。我们旨在通过研究从 CD14+单核细胞分化和成熟的未成熟树突状细胞(DC)来研究 CTD 对人髓样树突状细胞(DC)的影响。将 CTD 添加到起始 CD14+单核细胞的培养物中,会明显且呈剂量依赖性地降低收获的 DC 的活力。在 CTD 存在下分化的成熟 DC 的膜突比没有 CTD 的少且短。坏死细胞特征性形态变化也很明显。此外,CTD 影响 DC 分化和成熟表型,包括表面 CD1a、CD83 和 DC-SIGN 的下调。在 CTD 存在下衍生的 DC 在增殖和产生干扰素-γ方面对幼稚 CD4+CD45+RA+T 细胞的同种刺激活性受损。这表明 CTD 可能将 DC 分化重定向到更不成熟的阶段,而这种作用不仅仅是由于其细胞毒性。这种作用是否与免疫抑制或对疾病治疗的耐受性有关,需要进一步评估。

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