Choi Jung-Kyoung, Lee Seok-Geun, Lee Joo Yong, Nam Hae-Yun, Lee Woon-kyu, Lee Kweon-Haeng, Kim Hyung Jung, Lim Young
Catholic Neuroscience Center, the Catholic University of Korea, Seoul, Korea.
J Environ Pathol Toxicol Oncol. 2005;24(3):163-74. doi: 10.1615/jenvpathtoxoncol.v24.i3.30.
Silica is a causative factor of acute cell injury in pulmonary fibrosis. Inducible cyclooxygenase-2 (COX-2) was suggested to play a role in the process of inflammation and fibrosis. We report that silica induces COX-2 expression in WI-38 fibroblasts. Further analysis showed that silica activated the transcription of COX-2 gene primarily via a nuclear factor (NF)-kB binding site in the promoter. NF-kB-inducing kinase (NIK) and TGF-k activated kinase 1 (TAK1), the upstream signaling molecules of NF-kB, are involved in the silica-mediated COX-2 expression. The Electrophoretic Mobility Shift Assay (EMSA) showed that silica induced the direct binding of NF-kB on the putative binding site in COX-2 promoter. These results suggest that silica activates the human COX-2 gene transcription through the induction of NF-kB activity.
