TAK1-MAPK-NFκB signaling pathways regulates induction of TNF-α by wear particles in vitro
Purpose: Wear particles may induce inflammatory osteolysis by activating the nuclear factor κB (NFκB) and mitogen activated protein kinases (MAPKs). Previous studies have shown that transforming growth factor-beta activated kinase 1 (TAK1) functions as an adaptor molecule in the interaction between tumor necrosis factor receptor-associated factor 6(TRAF6) and downstream molecules such as NF-κB, p38 MAPK signaling cascades. This study investigated the roles of TAK1 pathway in TNF-α production after exposure to titanium particles.Methods: RAW 264.7 murine macrophages were incubated with endotoxin-free titanium particles in the presence and absence of TAK1 inhibitors 5Z-7-oxozeaenol. TAK1 activation was assessed with use of Western blot. p38MAPK and NFκB activation was evaluated by detecting endogenous levels of Phospho-p38α MAPK and Phospho-NFκBp65 protein using enzymelinked immunosorbent assay (ELISA).TNF-α mRNA and protein in cell culture medium was qualified using quantitative real time reverse transcriptase polymerase chain reaction and ELISA respectively. Results: Endogenous TAK1 was phosphorylated upon simulation of titanium particles in RAW 264.7 cells. We also showed that 5Z-7-oxozeaenol decreased the amount of phospho-p38α and phospho-NFκBp65 which were activated by LPS and the titanium particles. Furthermore, we demonstrated that TNF-α was completely blocked by the TAK1 inhibitor in RAW 264.7 cells. Conclusions: In the present study, we conclude that TAK1-MAPK-NFκB signaling pathways are involved in the induction of TNF-α in RAW264.7 cells exposed to titanium particles. These results suggest that TAK1-MAPK-NFκB signaling pathway may be a potential pharmacological target to modulate wear particle-induced inflammation.
titanium particle signaling pathway inflammation
Tao Cheng Xiaochun Peng Xianlong Zhang
Department of Orthopaedic Surgery,Shanghai Sixth Peoples Hospital,Medical College,Shanghai Jiaotong University Shanghai,China
国际会议
北京
英文
1-4
2009-06-11（万方平台首次上网日期，不代表论文的发表时间）