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

Citation
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
Citations number
25
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Immunology
Journal title
JOURNAL OF ENDOTOXIN RESEARCH
ISSN journal
0968-0519 → ACNP
Volume
7
Issue
3
Year of publication
2001
Pages
232 - 236
Database
ISI
SICI code
0968-0519(2001)7:3<232:IOTCIS>2.0.ZU;2-Z
Abstract
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.