Molecular and Cellular Biology, October 1999, p. 6471-6478, Vol. 19, No. 10
The Zena and Michael A. Wiener Cardiovascular
Institute and Department of Medicine, Mount Sinai School of Medicine,
New York, New York
Received 2 April 1999/Returned for modification 7 May 1999/Accepted 9 July 1999
Glucocorticoids are potent anti-inflammatory agents widely used in
the treatment of human disease. We have previously shown that the
inflammatory cytokine monocyte chemoattractant protein 1 (MCP-1) is
regulated posttranscriptionally by glucocorticoids in arterial smooth
muscle cells (SMC). To elucidate the mechanism mediating this effect,
in vitro-transcribed radiolabeled MCP-1 mRNA was incubated with
cytoplasmic extracts from SMC and analyzed by gel electrophoresis.
Extracts from SMC treated with platelet-derived growth factor (PDGF)
did not degrade the transcripts for up to 3 h. In contrast,
extracts from cells treated with 1 µM dexamethasone (Dex) alone or in
combination with PDGF degraded the probe with a half-life of
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Identification of a Novel Dexamethasone-Sensitive
RNA-Destabilizing Region on Rat Monocyte Chemoattractant Protein
1 mRNA
15 min.
Dex had maximal effect at concentrations above 0.01 µM and was
effective on both rat and human MCP-1 transcripts. By deletion
analysis, the Dex-sensitive region of the MCP-1 mRNA was localized to
the initial 224 nucleotides (nt) at the 5' end and did not involve an
AU-rich sequence in the 3' untranslated end. The 224-nt region
conferred Dex sensitivity to heterologous mRNA. These studies provide
new insights into the molecular mechanisms underlying the effect of
glucocorticoids on gene expression.
*
Corresponding author. Mailing address: Box 1030, Mount
Sinai School of Medicine, One Gustave L. Levy Place, New York, NY
10029. Phone: (212) 241-3913. Fax: (212) 987-3258. E-mail:
m_poon{at}smtplink.mssm.edu.
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