K. Kawasaki et al., Involvement of TLR4/MD-2 complex in species-specific lipopolysaccharide-mimetic signal transduction by Taxol, J ENDOTOX R, 7(3), 2001, pp. 232-236
Taxol, an antitumor agent derived from a plant,, mimics the action of lipop
olysaccharide (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 p
oint mutation in Toll-like receptor 4 (TLR4); therefore, TLR4 appears to be
involved in both Taxol and LPS signaling. In addition, TLR4 was recently s
hown to physically associate with MD-2, a molecule that confers LPS-respons
iveness 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 b
oth 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 f
or Taxol responsiveness, and that the TLR4/MD-2 complex is the shared molec
ule 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 M
D-2 is responsible for the species-specific responsiveness to Taxol.