• Hong-Jai Park, Ju-ho Hong, Hyung-Joon Kwon, Youngchan Kim, Kwan-Hee Lee, Jong-Bae Kim, and Seong K Song.
• Institute for Biomedical Research, Handong University, Namsong-ri 3, Heunghae-eup, Buk-gu, Pohang, Kyungbuk 791-708, South Korea.
• Biochem. Biophys. Res. Commun. 2010 Jun 4; 396 (3): 721-5.

AbstractKorean mistletoe lectin (KML-C) is an adjuvant that activates systemic and mucosal immune cells to release cytokines including TNF-alpha, which induces immunity against viruses and cancer cells. Although the immunomodulatory activity of KML-C has been well established, the underlying mechanism of action of KML-C has yet to be explored. When mouse peritoneal macrophages were treated with KML-C, both transcription and translation of TLR4 were upregulated. KML-C-induced TLR4 downstream events were similar to those activated by LPS: the upregulation of interleukin-1 receptor-associated kinase-1 (IRAK1); resulting in macrophage activation and TNF-alpha production. When TLR4 was blocked using a TLR4-specific neutralizing antibody, TNF-alpha production from the macrophages was significantly inhibited. Moreover, TLR4-deficient mouse macrophages treated with KML-C also secreted greatly reduced level of TNF-alpha secretion. Finally, TLR4 molecules were co-precipitated with KML-C, to which agarose beads were conjugated, indicating that those molecules are associated. These data indicate that KML-C activates mouse macrophages to secrete TNF-alpha by interacting with the TLR4 molecule and activating its signaling pathways.Copyright (c) 2010 Elsevier Inc. All rights reserved.

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