Silica induces human cyclooxygenase-2 gene expression through the NF-κB signaling pathway

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)-kappa B binding site in the promoter. NF-kappa B-inducing kinase (NIK) and TGF-kappa activated kinase 1 (TAK1), the upstream signaling molecules of NF-kappa B, are involved in the silica-mediated COX-2 expression. The Electrophoretic Mobility Shift Assay (EMSA) showed that silica induced the direct binding of NF-kappa B 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-kappa B activity.