Tumor necrosis factor alpha inhibits type I collagen synthesis through repressive CCAAT/enhancer-binding proteins Journal Article
| Authors: | Greenwel, P.; Tanaka, S.; Penkov, D.; Zhang, W.; Olive, M.; Moll, J.; Vinson, C.; Di Liberto, M.; Ramirez, F. |
| Article Title: | Tumor necrosis factor alpha inhibits type I collagen synthesis through repressive CCAAT/enhancer-binding proteins |
| Abstract: | Extracellular matrix (ECM) formation and remodeling are critical processes for proper morphogenesis, organogenesis, and tissue repair. The proinflammatory cytokine tumor necrosis factor alpha (TNF-α) inhibits ECM accumulation by stimulating the expression of matrix proteolytic enzymes and by downregulating the deposition of structural macromolecules such as type I collagen. Stimulation of ECM degradation has been linked to prolonged activation of jun gene expression by the cytokine. Here we demonstrate that TNF-α inhibits transcription of the gene coding for the α2 chain of type I collagen [α2(I) collagen] in cultured fibroblasts by stimulating the synthesis and binding of repressive CCAAT/enhancer proteins (C/EBPs) to a previously identified TNF-α-responsive element. This conclusion was based on the concomitant identification of C/EBPβ and C/EBPδ as TNF-α-induced factors by biochemical purification and expression library screening. It was further supported by the ability of the C/EBP-specific dominant-negative (DN) protein to block TNF-α inhibition of α2(I) collagen but not TNF-α stimulation of the MMP-13 protease. The DN protein also blocked TNF-α downregulation of the gene coding for the α1 chain of type I collagen. The study therefore implicates repressive C/EBPs in the TNF-α-induced signaling pathway that controls ECM formation and remodeling. |
| Keywords: | controlled study; dna-binding proteins; nonhuman; animal cell; cells, cultured; gene expression; morphogenesis; transcription, genetic; transfection; transcription factors; nuclear proteins; collagen type 1; extracellular matrix; gene expression regulation; cytokine; amino acid sequence; molecular sequence data; tumor necrosis factor alpha; kinetics; tumor necrosis factor-alpha; rna, messenger; recombinant proteins; collagen; fibroblast; fibroblasts; base sequence; binding protein; binding sites; proteinase; cytokine release; tissue repair; ccaat-enhancer-binding proteins; collagen synthesis; organogenesis; enhancer elements (genetics); humans; priority journal; article |
| Journal Title: | Molecular and Cellular Biology |
| Volume: | 20 |
| Issue: | 3 |
| ISSN: | 0270-7306 |
| Publisher: | American Society for Microbiology |
| Date Published: | 2000-02-01 |
| Start Page: | 912 |
| End Page: | 918 |
| Language: | English |
| DOI: | 10.1128/mcb.20.3.912-918.2000 |
| PUBMED: | 10629048 |
| PROVIDER: | scopus |
| PMCID: | PMC85208 |
| DOI/URL: | |
| Notes: | Export Date: 18 November 2015 -- Source: Scopus |
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