MyD88 is involved in the signalling pathway for Taxol-induced apoptosis and TNF-alpha expression in human myelomonocytic cells.
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.
Division of Cancer Pathobiology, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo 060-8638, Japan.
Jingxin
J
Wang
Masanobu
M
Kobayashi
Mingzhe
M
Han
Sungki
S
Choi
Masatoshi
M
Takano
Satoshi
S
Hashino
Junji
J
Tanaka
Takeshi
T
Kondoh
Ken-ichi
K
Kawamura
Masuo
M
Hosokawa
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation / Q000378:metabolism*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology*; D002450:Cell Communication; D006099:Granuloma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009000:Monocytes / Q000166:cytology*; D053594:Myeloid Differentiation Factor 88; D017239:Paclitaxel / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism*; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D000972:Antineoplastic Agents, Phytogenic; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; D017239:Paclitaxel