MCB
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Greenwel, P.
Right arrow Articles by Ramirez, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Greenwel, P.
Right arrow Articles by Ramirez, F.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, February 2000, p. 912-918, Vol. 20, No. 3
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Tumor Necrosis Factor Alpha Inhibits Type I Collagen Synthesis through Repressive CCAAT/Enhancer-Binding Proteins

Patricia Greenwel,1 Shizuko Tanaka,1 Dmitri Penkov,1 Wen Zhang,1 Michelle Olive,2,dagger Jonathan Moll,2 Charles Vinson,2 Maurizio Di Liberto,3 and Francesco Ramirez1,*

Brookdale Center, Department of Biochemistry and Molecular Biology, Mount Sinai School of Medicine, New York University, New York, New York 100291; Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 208922; and Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 100213

Received 20 August 1999/Returned for modification 16 September 1999/Accepted 5 November 1999

Extracellular matrix (ECM) formation and remodeling are critical processes for proper morphogenesis, organogenesis, and tissue repair. The proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha ) 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-alpha inhibits transcription of the gene coding for the alpha 2 chain of type I collagen [alpha 2(I) collagen] in cultured fibroblasts by stimulating the synthesis and binding of repressive CCAAT/enhancer proteins (C/EBPs) to a previously identified TNF-alpha -responsive element. This conclusion was based on the concomitant identification of C/EBPbeta and C/EBPdelta as TNF-alpha -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-alpha inhibition of alpha 2(I) collagen but not TNF-alpha stimulation of the MMP-13 protease. The DN protein also blocked TNF-alpha downregulation of the gene coding for the alpha 1 chain of type I collagen. The study therefore implicates repressive C/EBPs in the TNF-alpha -induced signaling pathway that controls ECM formation and remodeling.


* Corresponding author. Mailing address: Brookdale Center in the Department of Biochemistry and Molecular Biology, Mount Sinai School of Medicine, New York University, New York, NY 10029. Phone: (212) 241-7984. Fax: (212) 722-5999. E-mail: ramirf01{at}doc.mssm.edu.

dagger Present address: Unité INSERM 441, 33600 Pessac, France.


Molecular and Cellular Biology, February 2000, p. 912-918, Vol. 20, No. 3
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.



This article has been cited by other articles:




Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. J. Virol. Eukaryot. Cell
Microbiol. Mol. Biol. Rev. Clin. Vaccine Immunol. All ASM Journals

Copyright © 2000 by the American Society for Microbiology. All rights reserved.