Identification of a Novel Dexamethasone-Sensitive RNA-Destabilizing Region on Rat Monocyte Chemoattractant Protein 1 mRNA

AUTOR(ES)

Poon, Michael

FONTE

American Society for Microbiology

RESUMO

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 ≈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.

Documentos Relacionados

• RNA-destabilizing Factor Tristetraprolin Negatively Regulates NF-κB Signaling*
• Expression of monocyte chemoattractant protein 1 mRNA in human idiopathic pulmonary fibrosis.
• The destabilizing elements in the coding region of c-fos mRNA are recognized as RNA.
• Posttranscriptional regulation of urokinase receptor mRNA: identification of a novel urokinase receptor mRNA binding protein in human mesothelioma cells.
• Dexamethasone modulates rat renal brush border membrane phosphate transporter mRNA and protein abundance and glycosphingolipid composition.