Toll-like receptor 2 is at least partly involved in the antitumor activity of glycoprotein from Chlorella vulgaris

Int Immunopharmacol. 2002 Mar;2(4):579-89. doi: 10.1016/s1567-5769(02)00002-4.

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

  • Animals
  • Antineoplastic Agents, Phytogenic / isolation & purification*
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Cell Line
  • Chlorella / chemistry*
  • Drosophila Proteins*
  • Female
  • Gene Deletion
  • Gene Expression Regulation
  • Glycoproteins / isolation & purification*
  • Glycoproteins / pharmacology*
  • Humans
  • Interleukin-12 / biosynthesis
  • Interleukin-12 / chemistry
  • Interleukin-12 / genetics
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Inbred Strains
  • Mice, Knockout
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Spleen / cytology
  • Spleen / drug effects
  • Spleen / metabolism
  • Time Factors
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Toll-Like Receptors

Substances

  • Antineoplastic Agents, Phytogenic
  • Drosophila Proteins
  • Glycoproteins
  • Membrane Glycoproteins
  • RNA, Messenger
  • Receptors, Cell Surface
  • TLR2 protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • Interleukin-12