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Journal of Environmental Pathology, Toxicology and Oncology

ISSN for PRINT: 0731-8898

Institutional price:	$672.00
Issues per year:	4

Best Paper Award Selection - Editorial Board Site

2005, Volume24

98 pages

DOI: 10.1615/JEnvPathToxOncol.v24.i3

Issue price - $160.00

Silica Induces Human Cyclooxygenase-2 Gene Expression Through the NF-kB Signaling Pathway

Jung-Kyoung Choi
Catholic Neuroscience Center, the Catholic University of Korea, Seoul, Korea

Seok-Geun Lee
Catholic Neuroscience Center, the Catholic University of Korea, Seoul, Korea

Joo Yong Lee
Catholic Neuroscience Center, the Catholic University of Korea, Seoul, Korea

Hae-Yun Nam
Department of Occupational and Environmental Medicine, St. Mary's Hospital, the Catholic University of Korea, Seoul, Korea

Woon-kyu Lee
Department of Pharmacology, College of Medicine, the Catholic University of Korea, Seoul, Korea

Kweon-Haeng Lee
Catholic Neuroscience Center; and Department of Pharmacology, College of Medicine, the Catholic University of Korea, Seoul, Korea

Hyung Jung Kim
Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea

Young Lim
Department of Occupational and Environmental Medicine, St. Mary's Hospital, the Catholic University of Korea, Seoul, Korea

ABSTRACT

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.