Toll-like receptor 2 is at least partly involved in the antitumor activity of glycoprotein from Chlorella vulgaris.
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.
Hasegawa
Takashi
T
Research Laboratories, Chlorella Industry Co, Ltd, Chikugo City, Fukuoka, Japan. hasegawa@chlorella.co.jp
Matsuguchi
Tetsuya
T
Noda
Kiyoshi
K
Tanaka
Kuniaki
K
Kumamoto
Shoichiro
S
Shoyama
Yukihiro
Y
Yoshikai
Yasunobu
Y
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification* / Q000494:pharmacology*; D002460:Cell Line; D002708:Chlorella / Q000737:chemistry*; D029721:Drosophila Proteins; D005260:Female; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000302:isolation & purification* / Q000494:pharmacology*; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D000972:Antineoplastic Agents, Phytogenic; D029721:Drosophila Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D018664:Interleukin-12