Ginsenoside 20(R)-Rg3 enhances natural killer cell activity by increasing activating receptor expression through the MAPK/ERK signaling pathway

MAPK/ERK通路 细胞生物学 信号转导 穿孔素 自然杀伤细胞 激酶 NKG2D公司 化学 细胞毒性 生物 生物化学 体外
作者
Yunhee Lee,Arum Park,Young‐Jun Park,Haiyoung Jung,Tae‐Don Kim,Ji‐Yoon Noh,Inpyo Choi,Seungjin Lee,Suk Ran Yoon
出处
期刊:International Immunopharmacology [Elsevier BV]
卷期号:107: 108618-108618 被引量:24
标识
DOI:10.1016/j.intimp.2022.108618
摘要

Ginseng is one of the most widely used herbal remedies for various diseases worldwide. Ginsenoside Rg3 (G-Rg3), the main component of ginseng, possesses several pharmacological properties, including anti-inflammatory, anti-tumor, antioxidant, anti-obesity, and immunomodulatory activities. However, the effect of G-Rg3 on natural killer (NK) cells in humans is not fully understood. Here, we investigated the effect of G-Rg3 on NK cell function and differentiation and elucidated the underlying mechanism. G-Rg3 increased NK cell cytotoxicity and simultaneously increased the expression of NK-activating receptors, NKp44, NKp46, and NKp30. Additionally, G-Rg3 increased the mRNA expression of NK cytolytic molecules, granzyme B and perforin. The expression of CD107a, a marker of NK cell degranulation, also increased in G-Rg3-treated NK cells. We therefore proceeded to identify which MAPK signaling pathway was involved in G-Rg3-mediated cytolytic activity. Treatment with G-Rg3 increased the phosphorylation levels of extracellular signal-regulated kinase (ERK), whereas ERK inhibition eliminated G-Rg3-induced NK cell cytotoxicity, suggesting the involvement of the ERK pathway. G-Rg3 did not affect the rate of differentiation of human cord-blood-derived NK cells; however, it increased the functional maturation of differentiated NK cells and promoted their cytotoxicity. The G-Rg3 isomer, 20(R)-Rg3, effectively activated NK cells via the extracellular signal-regulated kinase (ERK) signaling pathway, whereas 20(S)-Rg3 had no effect on NK cell activity. Altogether, the results demonstrated that 20(R)-Rg3 promoted NK cell activity via activation of the MAPK/ERK pathway, suggesting that 20(R)-Rg3 may be used as an activator of NK cell cytotoxicity for the treatment of diverse types of cancers.
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