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灵芝通过诱导 NKG2D/NCR 的激活以及穿孔素和颗粒酶的分泌来刺激 NK 细胞的细胞毒性。

Ganoderma lucidum stimulates NK cell cytotoxicity by inducing NKG2D/NCR activation and secretion of perforin and granulysin.

机构信息

1Center for Molecular and Clinical Immunology, Chang Gung University, Taoyuan, Taiwan, Republic of China.

出版信息

Innate Immun. 2014 Apr;20(3):301-11. doi: 10.1177/1753425913491789. Epub 2013 Jun 26.

DOI:10.1177/1753425913491789
PMID:23803412
Abstract

Ganoderma lucidum (G. lucidum) is a medicinal mushroom long used in Asia as a folk remedy to promote health and longevity. Recent studies indicate that G. lucidum activates NK cells, but the molecular mechanism underlying this effect has not been studied so far. To address this question, we prepared a water extract of G. lucidum and examined its effect on NK cells. We observed that G. lucidum treatment increases NK cell cytotoxicity by stimulating secretion of perforin and granulysin. The mechanism of activation involves an increased expression of NKG2D and natural cytotoxicity receptors (NCRs), as well as increased phosphorylation of intracellular MAPKs. Our results indicate that G. lucidum induces NK cell cytotoxicity against various cancer cell lines by activating NKG2D/NCR receptors and MAPK signaling pathways, which together culminate in exocytosis of perforin and granulysin. These observations provide a cellular and molecular mechanism to account for the reported anticancer effects of G. lucidum extracts in humans.

摘要

灵芝(Ganoderma lucidum)是一种药用蘑菇,在亚洲长期以来被用作民间疗法,以促进健康和长寿。最近的研究表明,灵芝激活自然杀伤(NK)细胞,但这一作用的分子机制迄今尚未研究。为了解决这个问题,我们制备了灵芝的水提取物,并研究了其对 NK 细胞的作用。我们观察到灵芝处理通过刺激穿孔素和颗粒酶的分泌来增加 NK 细胞的细胞毒性。激活的机制涉及 NKG2D 和自然细胞毒性受体(NCR)的表达增加,以及细胞内 MAPK 的磷酸化增加。我们的结果表明,灵芝通过激活 NKG2D/NCR 受体和 MAPK 信号通路诱导 NK 细胞对各种癌细胞系的细胞毒性,最终导致穿孔素和颗粒酶的胞吐作用。这些观察结果为灵芝提取物在人类中报道的抗癌作用提供了一个细胞和分子机制。

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