MyD88 is involved in the signalling pathway for Taxol-induced apoptosis and TNF-alpha expression in human myelomonocytic cells

Br J Haematol. 2002 Aug;118(2):638-45. doi: 10.1046/j.1365-2141.2002.03645.x.

Abstract

Taxol is an effective anti-tumour drug against a variety of tumour cells. Taxol directly induces apoptosis in addition to a G2/M cell cycle arrest. However, it remains poorly understood how Taxol induces apoptosis in tumour cells. Taxol induces the secretion of inflammatory cytokines in murine macrophages in a toll-like receptor-4 (TLR-4)-dependent manner in addition to its anti-tumour effects, but the effect of Taxol on human macrophages is controversial. In this study, we demonstrated that low doses (less than 1000 nmol/l) of Taxol induced the expression of tumour necrosis factor (TNF)-alpha in human myelomonocytic cells and that the induction of TNF-alpha mRNA was inhibited by dominant-negative myeloid differentiation protein (dnMyD88). Furthermore, we demonstrated that the same doses of Taxol induced apoptosis of the same myelomonocytic cells and that the Taxol-induced apoptosis was also inhibited by dnMyD88. In accordance with the previous reports, Taxol induced the expression of TNF-alpha and apoptosis in a TLR4-independent manner. These results suggest that TNF-alpha expression and apoptosis, both induced by Taxol in human myelomonocytic cells, share the signal transduction molecule MyD88.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Antigens, Differentiation / metabolism*
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Bone Marrow Cells / cytology*
  • Cell Communication
  • Granuloma / metabolism
  • Granuloma / pathology
  • Humans
  • Monocytes / cytology*
  • Myeloid Differentiation Factor 88
  • Paclitaxel / pharmacology*
  • RNA, Messenger / metabolism
  • Receptors, Immunologic / metabolism*
  • Signal Transduction
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Antigens, Differentiation
  • Antineoplastic Agents, Phytogenic
  • MYD88 protein, human
  • Myeloid Differentiation Factor 88
  • RNA, Messenger
  • Receptors, Immunologic
  • Tumor Necrosis Factor-alpha
  • Paclitaxel