Abstract
Toll-like receptors (TLR) are involved in innate immunity by recognizing various bacterial components. We have previously reported that an active substance of ARS-2 purified from the culture medium of Chlorella vulgaris was a glycoprotein with a molecular weight of 63,100 amu and that this glycoprotein expressed antitumor activity, with the protein moiety in ARS-2 being necessary for this antitumor activity. Here, we show that ARS-2 stimulated spleen-adherent cells from C3H/HeJ lacking functional TLR4 to produce interleukin-12 (IL-12) p40, whereas such cytokine production was significantly impaired in ARS-2-stimulated spleen-adherent cells from TLR2 knockout mice. The overexpression of mouse TLR2 (mTLR2) and mouse CD14 (mCD14) conferred the ARS-2 inducibility of nuclear factor-kappaB activation to human HEK 293 cells. These results suggest that TLR2 signaling is at least partly involved in the antitumor activity of the water-soluble antitumor glycoprotein from C. vulgaris.
MeSH terms
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Animals
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Antineoplastic Agents, Phytogenic / isolation & purification*
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Antineoplastic Agents, Phytogenic / pharmacology*
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Cell Line
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Chlorella / chemistry*
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Drosophila Proteins*
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Female
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Gene Deletion
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Gene Expression Regulation
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Glycoproteins / isolation & purification*
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Glycoproteins / pharmacology*
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Humans
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Interleukin-12 / biosynthesis
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Interleukin-12 / chemistry
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Interleukin-12 / genetics
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / metabolism*
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Mice
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Mice, Inbred Strains
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Mice, Knockout
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / metabolism*
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Spleen / cytology
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Spleen / drug effects
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Spleen / metabolism
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Time Factors
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Toll-Like Receptor 2
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Toll-Like Receptor 4
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Toll-Like Receptors
Substances
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Antineoplastic Agents, Phytogenic
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Drosophila Proteins
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Glycoproteins
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Membrane Glycoproteins
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RNA, Messenger
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Receptors, Cell Surface
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TLR2 protein, human
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TLR4 protein, human
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Toll-Like Receptor 2
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Toll-Like Receptor 4
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Toll-Like Receptors
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Interleukin-12