Document Detail

Up-regulation of matrix metalloproteinase-1 expression in U937 cells by low-density lipoprotein-containing immune complexes requires the activator protein-1 and the Ets motifs in the distal and the proximal promoter regions.
MedLine Citation:
PMID:  12871225     Owner:  NLM     Status:  MEDLINE    
We reported previously that low-density lipoprotein (LDL)-containing immune complexes (LDL-IC) stimulated matrix metalloproteinase-1 (MMP-1) expression in U937 histiocytes through Fc gamma receptor (FcgammaR)-mediated extracellular signal-regulated kinase pathway. The present study has explored the transcriptional mechanisms involved in the stimulation. Deletion analysis showed that LDL-IC stimulated MMP-1 promoter activity in cells transfected with the Construct 1 that contained a 4,334-bp MMP-1 promoter fragment, but had no effect in cells transfected with other constructs that had shorter MMP-1 promoter (2685-bp or less), suggesting that cis-acting elements located between -4334 and -2685 are required for the promoter stimulation. The mutation study further indicated that the activator protein-1 (AP-1) (-3471) or Ets (-3836) motifs in this distal region were essential for the LDL-IC-stimulated MMP-1 expression. Moreover, although above deletion analysis showed that LDL-IC did not stimulate MMP-1 promoter activity in cells transfected with constructs that contained the proximal AP-1 (-72) and Ets (-88) in the promoter fragments that are 2685-bp or less, the mutations of the -72 AP-1 or the -88 Ets motif in the construct 1 abolished the stimulation of MMP-1 expression by LDL-IC, suggesting that a long promoter sequence is required for the -72 AP-1 and -88 Ets motifs to be involved in the stimulation. Finally, electrophoretic mobility shift assay showed that LDL-IC stimulated the activities of transcription factors AP-1 and Ets. In conclusion, the present study shows that both the distal and proximal AP-1 and Ets motifs are required for LDL-IC-stimulated MMP-1 expression in U937 histiocytes.
Alejandro Maldonado; Bryan A Game; Lanxi Song; Yan Huang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Immunology     Volume:  109     ISSN:  0019-2805     ISO Abbreviation:  Immunology     Publication Date:  2003 Aug 
Date Detail:
Created Date:  2003-07-21     Completed Date:  2003-09-16     Revised Date:  2013-06-09    
Medline Journal Info:
Nlm Unique ID:  0374672     Medline TA:  Immunology     Country:  England    
Other Details:
Languages:  eng     Pagination:  572-9     Citation Subset:  IM    
Division of Endocrinology, Diabetes and Medical Genetics, Department of Medicine, Medical University of South Carolina, Charleston, SC 29403, USA.
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MeSH Terms
Antigen-Antibody Complex / immunology*
Base Sequence
Blotting, Northern / methods
DNA / analysis
Electrophoretic Mobility Shift Assay / methods
Enzyme-Linked Immunosorbent Assay / methods
Gene Deletion
Lipoproteins, LDL / immunology*
Matrix Metalloproteinase 1 / genetics*,  immunology
Mutation / genetics,  immunology
Promoter Regions, Genetic / immunology*
Proto-Oncogene Proteins / genetics,  immunology
Proto-Oncogene Proteins c-ets
Transcription Factor AP-1 / immunology*
Transcription Factors / genetics,  immunology
Transcription, Genetic
U937 Cells
Up-Regulation / immunology*
Reg. No./Substance:
0/Antigen-Antibody Complex; 0/Lipoproteins, LDL; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-ets; 0/Transcription Factor AP-1; 0/Transcription Factors; 9007-49-2/DNA; EC Metalloproteinase 1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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