title: Silica induces nuclear factor-kappaB activation through TAK1 and NIK in Rat2 cell line.
abstract: Silica has been known to be a factor in acute cell injury and chronic pulmonary fibrosis. In Rat2 fibroblasts, silica induced the activation of nuclear factor-kappa B (NF-kappaB), which plays a crucial role in regulating the expression of many genes involved in the subsequent inflammatory response. In addition, we observed that transforming growth factor-beta activated kinase 1 (TAK1) and NF-kappaB-inducing kinase (NIK) were involved in silica-mediated NF-kappaB activation in Rat2 cells. The dominant negative mutant forms of TAK1 and NIK inhibited the silica-induced NF-kappaB activation in Rat2 cells. Furthermore, we demonstrated that endogenous TAK1 is phosphorylated in silica-stimulated Rat2 cells. These results indicate that TAK1 functions as a critical mediator in the silica-induced signaling pathway.
authors.affiliation: Department of Occupational and Environmental Medicine, College of Medicine, The Catholic University of Korea, Youngdunpo-gu, Seoul, South Korea.
authors.forename: HyeYoung
authors.initials: H
authors.lastname: Cho
authors.forename: JooYong
authors.initials: J
authors.lastname: Lee
authors.forename: Noh-Jin
authors.initials: NJ
authors.lastname: Kwak
authors.forename: Kweo-Haeng
authors.initials: KH
authors.lastname: Lee
authors.forename: SukJoo
authors.initials: S
authors.lastname: Rha
authors.forename: Young-Hoon
authors.initials: YH
authors.lastname: Kim
authors.forename: Yong-Yeun
authors.initials: YY
authors.lastname: Cho
authors.forename: Ki-Hwa
authors.initials: KH
authors.lastname: Yang
authors.forename: KyoungAh
authors.initials: K
authors.lastname: Kim
authors.forename: Young
authors.initials: Y
authors.lastname: Lim
mesh_terms: D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D012822:Silicon Dioxide / Q000633:toxicity*; D014162:Transfection; D000097782:NF-kappaB-Inducing Kinase; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D008156:Luciferases; D020930:MAP Kinase Kinase Kinases; D016328:NF-kappa B; D017346:Protein Serine-Threonine Kinases; D012822:Silicon Dioxide; D000097782:NF-kappaB-Inducing Kinase; D000099151:MAP Kinase Kinase Kinase 7