Extracellular Signal-Regulated Kinase Is a Major Enzyme in Korean Mistletoe Lectin-Mediated Regulation of Macrophage Functions

Abstract

-Korean mistletoe lectin (KML) is the major component found in Viscum album var. (coloratum), displaying anti-cancer and immunostimulating activities. Even though it has been shown to boost host immune defense mechanisms, the regulatory roles of KML on the functional activation of macrophages have not been fully elucidated. In this study, regulatory mechanism of KML on macrophage-mediated immune responses was examined in terms of KML-mediated signaling event. KML clearly induced mRNA expression of tumor necrosis factor (TNF)-α, the generation of reactive oxygen species (ROS) and phagocytic uptake in RAW264.7 cells. All of these events were strongly suppressed by U0126, whereas TNF-α mRNA was not diminished by SB203580 and SP600125, indicating ERK as a central enzyme managing KML-induced up-regulation of macrophage functions. Indeed, KML strongly induced the phosphorylation of ERK in a time-dependent manner without altering its total level. Therefore, these data suggest that ERK may be a major signaling enzyme with regulatory property toward various KML-mediated macrophage responses.

The Anti-Inflammatory Activity of Viscum album

“…The V. album extracts display their action as phytocomplex, wherein besides the microProteins such as viscotoxins and viscolectins, they act with extracellular signal-regulated enzymes [ 286 , 287 ], as well many other constituents that can take part in the main property, antioxidant, anti-inflammatory and anti-stress activity, which contributes to the general actions in restoring or maintaining homeostasis. Particular attention should be concentrated on the constituents of the metabolome, including the discovery of new active constituents that are very different from microProteins [ 288 ].…”