title: Transforming growth factor-beta activated kinase 1 signaling pathways regulate TNF-alpha production by titanium alloy particles in RAW 264.7 cells.
abstract: Implant particles may induce inflammatory response by activating the nuclear factor kappaB (NFkappaB) and mitogen activated protein kinases (MAPK). Previous studies have shown that these signaling pathways are involved in the transforming growth factor-beta activated kinase 1 (TAK1) in signaling cascades induced by the receptor activator of NFkappaB ligand (RANKL) and tumor necrosis factor-alpha (TNF-alpha) as well as interleukin-1beta (IL-1beta). In this study, the roles of the TAK1 pathway in the production of the pro-inflammatory cytokine TNF-alpha in RAW 264.7 cells exposed to titanium alloy particles were investigated. Endogenous TAK1 was phosphorylated upon simulating RAW 264.7 cells by titanium alloy particles. The critical role for TAK1 in p38MAPK and NFkappaB activation was as well confirmed by the inhibition of p38MAPK and NFkappaB activity following 5Z-7-oxozeaenol, a selective inhibitor of TAK1. Furthermore, it was found that TNF-alpha was completely blocked by 5Z-7-oxozeaenol in RAW 264.7 cells. These results suggest that the TAK1-MAPK-NFkappaB signaling pathways may be a potential pharmacological target that can prevent instability for arthroplasty prosthesis.
authors.affiliation: Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200233, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Cheng
authors.forename: Xiao-Chun
authors.initials: XC
authors.lastname: Peng
authors.forename: Feng-Feng
authors.initials: FF
authors.lastname: Li
authors.forename: Xian-Long
authors.initials: XL
authors.lastname: Zhang
authors.forename: Kong-Zu
authors.initials: KZ
authors.lastname: Hu
authors.forename: Jun-Feng
authors.initials: JF
authors.lastname: Zhu
authors.forename: Bing-Fang
authors.initials: BF
authors.lastname: Zeng
mesh_terms: D000497:Alloys / Q000737:chemistry*; D000818:Animals; D001178:Arthroplasty / Q000379:methods; D002460:Cell Line; D007249:Inflammation; D008070:Lipopolysaccharides / Q000737:chemistry; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000166:cytology; D051379:Mice; D010766:Phosphorylation; D015398:Signal Transduction; D014025:Titanium / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D015025:Zearalenone / Q000031:analogs & derivatives / Q000494:pharmacology / Q000008:administration & dosage; D000099151:MAP Kinase Kinase Kinase 7; D007783:Lactones; D012118:Resorcinols
chemical_list: D000497:Alloys; D008070:Lipopolysaccharides; D020930:MAP Kinase Kinase Kinases; D014025:Titanium; D014409:Tumor Necrosis Factor-alpha; D015025:Zearalenone; D000099151:MAP Kinase Kinase Kinase 7; C505734:7-oxozeanol; D007783:Lactones; D012118:Resorcinols