Cho HyeYoung, Lee JooYong, Kwak Noh-Jin, Lee Kweo-Haeng, Rha SukJoo, Kim Young-Hoon, Cho Yong-Yeun, Yang Ki-Hwa, Kim KyoungAh, Lim Young
Department of Occupational and Environmental Medicine, College of Medicine, The Catholic University of Korea, Youngdunpo-gu, Seoul, South Korea.
Toxicol Lett. 2003 Aug 28;143(3):323-30. doi: 10.1016/s0378-4274(03)00193-0.
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.
