Egr-1 mediates Si0(2)-driven transcription of membrane type I matrix metalloproteinase in macrophages.
The up-regulation mechanism of membrane type I matrix metalloproteinase (MT1-MMP) in macrophages stimulated by silica in vitro and the contribution of early growth response 1 (Egr-1) transcription factor in the gene expression pathway were investigated. Macrophages stimulated by silica were treated with Egr-1 antibody or Egr-1 decoy oligodeoxynucleotides (ODN). The levels of MT1-MMP proteins were determined by Western blot and the expression of MT1-MMP mRNAs was detected by RT-PCR. The results showed as compared with control macrophages, silica-stimulated group showed up-regulated gene expression of MT1-MMP via Egr-1 (P<0.01). Compared with silica-stimulated macrophages untreated with antibody, the cells treated with 5 microg/mL Egr-1 antibody were associated with reduced expression of MT1-MMP protein (P<0.01) and mRNA (P<0.01). Compared with silica-stimulated untransfected group, the Egr-1 "decoy" ODN group was associated with reduction in the expression of MT1-MMP protein and mRNA (P<0.01). It was concluded gene expression of MT1-MMP which may play a critical role in silicosis was up-regulated by silica in macrophages. Egr-1 participated in the expression of MT1-MMP and positively regulated the expression. Both Egr-1 antibody and Egr-1 decoy ODN suppressed the expression of MT1-MMP through the Egr-1 pathway and may become a potential therapeutic tool in the management of silicosis in the future.
Xiang
Fei
F
Department of Respiratory Medicine, Unton Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. fly-x@sohu.com
Bai
Ming
M
Jin
Yang
Y
Ma
Wanli
W
Xin
Jianbao
J
D000818:Animals; D002460:Cell Line; D051766:Early Growth Response Protein 1 / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D008264:Macrophages / Q000378:metabolism*; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism*; D051379:Mice; D010957:Plasmids; D012822:Silicon Dioxide / Q000378:metabolism*; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection
D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D012822:Silicon Dioxide; D053511:Matrix Metalloproteinase 14