Suppressive effect of a standardized mistletoe extract on the expression of activatory NK receptors and function of human NK cells.
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.
Lee
Soo Jung
SJ
Department of Biochemistry, Pusan National University School of Medicine, Busan, Korea.
Son
Young-Ok
YO
Kim
Hyunjin
H
Kim
Joo-Young
JY
Park
Soon-Won
SW
Bae
Jae-Ho
JH
Kim
Hyung Hoi
HH
Lee
Eun-Yup
EY
Chung
Byung-Seon
BS
Kim
Sun-Hee
SH
Kang
Chi-Dug
CD
D000818:Animals; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D015536:Down-Regulation / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D014784:Mistletoe / Q000276:immunology*; D055655:NK Cell Lectin-Like Receptor Subfamily K; D010936:Plant Extracts / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000235:genetics; D055607:Receptors, Natural Killer Cell
D007166:Immunosuppressive Agents; C527085:KLRK1 protein, human; C527086:Klrk1 protein, mouse; D055655:NK Cell Lectin-Like Receptor Subfamily K; D010936:Plant Extracts; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell