HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 285/6/C1349    most recent 00173.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (13) Citing Articles via Google Scholar Google Scholar Articles by Kuang, P.-P. Articles by Goldstein, R. H. Search for Related Content PubMed PubMed Citation Articles by Kuang, P.-P. Articles by Goldstein, R. H.

EXTRACELLULAR MATRIX, CELL INTERACTIONS

Regulation of elastin gene transcription by interleukin-1-induced C/EBP isoforms

Pulmonary Center and Department of Biochemistry, Boston University School of Medicine, and Boston Department of Veterans Affairs Medical Center, Boston, Massachusetts 02118

Submitted 1 May 2003 ; accepted in final form 21 July 2003

We previously showed that interleukin (IL)-1 decreases elastin gene transcription through activation of the NF-B subunit p65 in neonatal rat lung fibroblasts. The present study was undertaken to further explore the molecular mechanisms responsible for the inhibitory effect of IL-1 on elastin gene transcription. We found that cycloheximide blocked IL-1-induced downregulation of elastin mRNA but did not inhibit IL-1-induced translocation of p65 into the nucleus. IL-1 treatment increased CCAAT/enhancer-binding protein (C/EBP) mRNA and protein levels including liver-enriched activating protein (LAP) and liver-enriched inhibitory protein (LIP), which was cycloheximide sensitive. C/EBP isoforms bound a GCAAT-containing sequence in the proximal elastin promoter as determined by electrophoretic gel shift studies and confirmed by using specific anti-C/EBP antibodies and by competition studies with oligonucleotides. Transient transfection of LIP expression vectors strongly decreased the transcriptional activity of the cotransfected elastin promoter and decreased levels of endogenous elastin mRNA. We demonstrated that IL-1-induced downregulation of elastin mRNA is dependent on NF-B activation and C/EBP expression. These results indicate that IL-1 treatment activates NF-B, which subsequently induces LIP expression and inhibition of elastin gene transcription.

lung; fibroblasts; emphysema; nuclear factor-B

This article has been cited by other articles:

				P.-P. Kuang, X.-H. Zhang, C. B. Rich, J. A. Foster, M. Subramanian, and R. H. Goldstein Activation of elastin transcription by transforming growth factor-beta in human lung fibroblasts Am J Physiol Lung Cell Mol Physiol, April 1, 2007; 292(4): L944 - L952. [Abstract] [Full Text] [PDF]

				R. A. Pierce, C. H. Moore, and M. C. Arikan Positive transcriptional regulatory element located within exon 1 of elastin gene. Am J Physiol Lung Cell Mol Physiol, September 1, 2006; 291(3): L391 - L399. [Abstract] [Full Text] [PDF]

				P.-P. Kuang, E. Lucey, D. C. Rishikof, D. E. Humphries, D. Bronsnick, and R. H. Goldstein Engraftment of Neonatal Lung Fibroblasts into the Normal and Elastase-Injured Lung Am. J. Respir. Cell Mol. Biol., October 1, 2005; 33(4): 371 - 377. [Abstract] [Full Text] [PDF]

				P.-P. Kuang and R. H. Goldstein Regulation of elastin gene transcription by proteasome dysfunction Am J Physiol Cell Physiol, September 1, 2005; 289(3): C766 - C773. [Abstract] [Full Text] [PDF]

				G. A. Darnell, T. M. Antalis, B. R. Rose, and A. Suhrbier Silencing of Integrated Human Papillomavirus Type 18 Oncogene Transcription in Cells Expressing SerpinB2 J. Virol., April 1, 2005; 79(7): 4246 - 4256. [Abstract] [Full Text] [PDF]

				U. Lappalainen, J. A. Whitsett, S. E. Wert, J. W. Tichelaar, and K. Bry Interleukin-1{beta} Causes Pulmonary Inflammation, Emphysema, and Airway Remodeling in the Adult Murine Lung Am. J. Respir. Cell Mol. Biol., April 1, 2005; 32(4): 311 - 318. [Abstract] [Full Text] [PDF]