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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Binding Sites / drug effects
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Cell Line
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Cyclooxygenase 2
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Dose-Response Relationship, Drug
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Enzyme Induction
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Fibroblasts / drug effects*
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Fibroblasts / enzymology
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Gene Expression Regulation, Enzymologic / drug effects*
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Humans
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MAP Kinase Kinase Kinases / metabolism
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Membrane Proteins
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NF-kappa B / metabolism*
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NF-kappaB-Inducing Kinase
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Prostaglandin-Endoperoxide Synthases / genetics*
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Prostaglandin-Endoperoxide Synthases / metabolism
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Protein Serine-Threonine Kinases / metabolism
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RNA, Messenger / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction
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Silicon Dioxide / toxicity*
Substances
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Membrane Proteins
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NF-kappa B
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RNA, Messenger
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Silicon Dioxide
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Cyclooxygenase 2
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PTGS2 protein, human
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Prostaglandin-Endoperoxide Synthases
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Protein Serine-Threonine Kinases
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MAP Kinase Kinase Kinases
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MAP kinase kinase kinase 7