Silica induces human cyclooxygenase-2 gene expression through the NF-kappaB 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)-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.
Choi
Jung-Kyoung
JK
Catholic Neuroscience Center, the Catholic University of Korea, Seoul, Korea.
Lee
Seok-Geun
SG
Lee
Joo Yong
JY
Nam
Hae-Yun
HY
Lee
Woon-kyu
WK
Lee
Kweon-Haeng
KH
Kim
Hyung Jung
HJ
Lim
Young
Y
D001665:Binding Sites / Q000187:drug effects; D002460:Cell Line; D051546:Cyclooxygenase 2; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D008565:Membrane Proteins; D016328:NF-kappa B / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D012822:Silicon Dioxide / Q000633:toxicity*; D000097782:NF-kappaB-Inducing Kinase; D000099151:MAP Kinase Kinase Kinase 7
D051546:Cyclooxygenase 2; D020930:MAP Kinase Kinase Kinases; D008565:Membrane Proteins; D016328:NF-kappa B; D011451:Prostaglandin-Endoperoxide Synthases; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D012822:Silicon Dioxide; D000097782:NF-kappaB-Inducing Kinase; D000099151:MAP Kinase Kinase Kinase 7; C496540:PTGS2 protein, human