In vitro immunoregulatory effects of Korean mistletoe lectin on functional activation of monocytic and macrophage-like cells.
Korean mistletoe lectin (KML) is one of the major active components in Viscum album var. (coloratum), displaying various biological effects such as anti-tumor and anti-metastatic activities. Even though it has been shown to boost host immune defense mechanisms, the immunomodulatory effects of KML on specific immune responses mediated by macrophages have not been fully elucidated. Therefore, in this study, we aimed to demonstrate KML's regulatory roles on macrophage-mediated immune responses. KML clearly blocked lipopolysaccharide (LPS)-induced events [expression of interleukin (IL)-10, nitric oxide (NO) production and phagocytic uptake], and suppressed the normal expression levels of IL-10 (at 2 ng/ml) and tumor necrosis factor (TNF)-alpha (at 10 ng/ml). In contrast, (1) the expression of cytokine (TNF-alpha) and (2) the generation of reactive oxygen species (ROS) induced by LPS were significantly up-regulated with KML co-treatment. In addition, KML itself increased the mRNA levels of IL-3 and IL-23; phagocytic uptake; the surface levels of co-stimulatory molecules (CD80 and CD86), pattern recognition receptors (PRRs) [such as dectin-1 and toll like receptor (TLR)-2] and adhesion molecules [beta1-integrins (CD29) and CD43]; and CD29-mediated cell adhesion events. Finally, according to co-treatment of D-galactose with KML under LPS-induced NO production conditions, KML inhibition seems to be mediated by binding to proteins with D-galactose. Therefore, these data suggest that KML may participate in regulating various macrophage-mediated innate and adaptive responses via binding to surface protein with D-galactose and that some of these may deserve in KML's therapeutic activities such as anti-tumor and anti-microbial effects.
Lee
Ji Yeon
JY
School of Bioscience and Biotechnology, and Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon, Korea.
Kim
Joo Young
JY
Lee
Yong Gyu
YG
Byeon
Se Eun
SE
Kim
Byung Hun
BH
Rhee
Man Hee
MH
Lee
Albert
A
Kwon
Moosik
M
Hong
Sungyoul
S
Cho
Jae Youl
JY
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D019012:Integrin beta1 / Q000378:metabolism; D019169:Jurkat Cells; D037102:Lectins / Q000494:pharmacology*; D037181:Lectins, C-Type; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D014784:Mistletoe; D009000:Monocytes / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D010587:Phagocytosis / Q000187:drug effects; D010946:Plants, Medicinal; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D020298:U937 Cells; D000099181:Dectin-1
D019012:Integrin beta1; D037102:Lectins; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009569:Nitric Oxide; D017382:Reactive Oxygen Species; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D000099181:Dectin-1; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse