Lee Soo Jung, Son Young-Ok, Kim Hyunjin, Kim Joo-Young, Park Soon-Won, Bae Jae-Ho, Kim Hyung Hoi, Lee Eun-Yup, Chung Byung-Seon, Kim Sun-Hee, Kang Chi-Dug
Department of Biochemistry, Pusan National University School of Medicine, Busan, Korea.
J Clin Immunol. 2007 Sep;27(5):477-85. doi: 10.1007/s10875-007-9098-7. Epub 2007 May 25.
Despite long-term use of mistletoe extracts for cancer treatment, their mode of action remains elusive. In this study, it was studied in vitro if mistletoe extract is able to modulate the expression of natural cytotoxic receptors (NCRs) and NKG2D receptor, which stimulate natural killer cell-mediated cytotoxicity. Unexpectedly, a mistletoe extract, ABNOBA viscum Fraxini, inhibited the expression level of NKp46 and NKG2D receptors in dose- and time-dependent manners. The levels of NKp30 and NKG2D receptors were remarkably induced and NKp44 was slightly induced after 48 h treatment with IL-2 and IL-15 in both mRNA and surface expression. The activatory NK receptors were not induced significantly after treatment with IL-12, IL-18, and IL-21 for 48 h. Induction of activatory NK receptors by IL-2 and IL-15 was suppressed almost to the untreated levels by treatment with mistletoe extract, which appeared to induce apoptosis of NK cells in a dose-dependent manner. However, the treatment with IL-2 and IL-15 did not prevent the mistletoe-induced NK-cell death. Mistletoe extract inhibited significantly the cytotoxic activity of resting and IL-2- or IL-15-stimulated NK cells. These results suggest that inhibition of survival and function of NK cells by mistletoe extract may curtail in part the therapeutic effects of mistletoe.
尽管长期使用槲寄生提取物治疗癌症，但其作用机制仍不清楚。在本研究中，对槲寄生提取物是否能够调节刺激自然杀伤细胞介导的细胞毒性的自然细胞毒性受体（NCRs）和NKG2D受体的表达进行了体外研究。出乎意料的是，一种槲寄生提取物ABNOBA viscum Fraxini以剂量和时间依赖性方式抑制NKp46和NKG2D受体的表达水平。在用IL-2和IL-15处理48小时后，NKp30和NKG2D受体的水平在mRNA和表面表达上均显著诱导，而NKp44略有诱导。在用IL-12、IL-18和IL-21处理48小时后，活化性NK受体未被显著诱导。用槲寄生提取物处理后，IL-2和IL-15对活化性NK受体的诱导几乎被抑制到未处理水平，槲寄生提取物似乎以剂量依赖性方式诱导NK细胞凋亡。然而，用IL-2和IL-15处理并不能阻止槲寄生诱导的NK细胞死亡。槲寄生提取物显著抑制静息以及IL-2或IL-15刺激的NK细胞的细胞毒性活性。这些结果表明，槲寄生提取物对NK细胞存活和功能的抑制可能部分削弱了槲寄生的治疗效果。
