Involvement of TLR4/MD-2 complex in species-specific lipopolysaccharide-mimetic signal transduction by Taxol

J Endotoxin Res. 2001;7(3):232-6.


Taxol, an antitumor agent derived from a plant, mimics the action of lipopolysaccharide (LPS) in mice, but not in humans. The LPS-mimetic activity of Taxol is not observed in LPS-hyporesponsive C3H/HeJ mice which possess a point mutation in Toll-like receptor 4 (TLR4); therefore, TLR4 appears to be involved in both Taxol and LPS signaling. In addition, TLR4 was recently shown to physically associate with MD-2, a molecule that confers LPS-responsiveness on TLR4. Here we examined whether or not TLR4/MD-2 complex mediates a Taxol-induced signal by using transformants of the mouse pro-B cell line, Ba/F3, expressing mouse TLR4 alone, both mouse TLR4 and mouse MD-2, and both mouse MD-2 and mouse TLR4 lacking the cytoplasmic portion. Our results demonstrated that co-expression of mouse TLR4 and mouse MD-2 was required for Taxol responsiveness, and that the TLR4/MD-2 complex is the shared molecule in Taxol and LPS signal transduction in mice. We also found that mouse MD-2, but not human MD-2, is involved in Taxol signaling, suggesting that MD-2 is responsible for the species-specific responsiveness to Taxol.

MeSH terms

  • Animals
  • Antigens, Surface / genetics
  • Antigens, Surface / immunology*
  • Antineoplastic Agents, Phytogenic / immunology*
  • Cell Line
  • Culture Media, Serum-Free
  • Drosophila Proteins*
  • Gene Expression
  • Humans
  • Lipid A / analogs & derivatives*
  • Lipid A / pharmacology
  • Lipopolysaccharides / immunology*
  • Lymphocyte Antigen 96
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology*
  • Mice
  • Molecular Mimicry / immunology*
  • NF-kappa B / antagonists & inhibitors
  • Paclitaxel / immunology*
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / immunology*
  • Signal Transduction / immunology*
  • Species Specificity
  • Toll-Like Receptor 4
  • Toll-Like Receptors


  • Antigens, Surface
  • Antineoplastic Agents, Phytogenic
  • B 464
  • Culture Media, Serum-Free
  • Drosophila Proteins
  • LY96 protein, human
  • Lipid A
  • Lipopolysaccharides
  • Lymphocyte Antigen 96
  • Membrane Glycoproteins
  • NF-kappa B
  • Receptors, Cell Surface
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • Paclitaxel