Suppressive Effect of a Standardized Mistletoe Extract on the Expression of Activatory NK Receptors and Function of Human NK Cells |
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Authors: | Soo Jung Lee Young-Ok Son Hyunjin Kim Joo-Young Kim Soon-Won Park Jae-Ho Bae Hyung Hoi Kim Eun-Yup Lee Byung-Seon Chung Sun-Hee Kim Chi-Dug Kang |
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Affiliation: | (1) Department of Biochemistry, Pusan National University School of Medicine, Busan, Korea;(2) Department of Laboratory Medicine, Pusan National University School of Medicine, Busan, Korea;(3) Medical Research Center for Ischemic Tissue Regeneration, Pusan National University School of Medicine, Busan, Korea;(4) Busan Regional Cancer Center, Pusan National University Hospital, Busan, Korea;(5) Medical Research Institute, Pusan National University, Busan, Korea;(6) Research and Development Center, Binex Co., Ltd., Busan, Korea;(7) Department of Biochemistry, School of Medicine, Pusan National University, Busan, 602-739, Korea |
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Abstract: | 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. Soo Jung Lee, Young-Ok Son, and Hyunjin Kim contributed equally to this article |
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Keywords: | Mistletoe NK cells NCR NKG2D receptor |
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