MyD88 is involved in the signalling pathway for Taxol-induced apoptosis and TNF-alpha expression in human myelomonocytic cells |
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Authors: | Wang Jingxin Kobayashi Masanobu Han Mingzhe Choi Sungki Takano Masatoshi Hashino Satoshi Tanaka Junji Kondoh Takeshi Kawamura Ken-ichi Hosokawa Masuo |
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Affiliation: | Division of Cancer Pathobiology, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo 060-8638, Japan. |
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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. |
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Keywords: | taxol MyD88 apoptosis TNF-α signal transduction toll-like receptor |
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