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Glucocorticoids inhibit E-selectin expression by targeting NF-kappaB and not ATF/c-Jun
C Brostjan1, J Anrather, V Csizmadia
1Sandoz Center for Immunobiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|April 15, 1997
Summary
Dexamethasone, a potent anti-inflammatory drug, reduces E-selectin expression by inhibiting transcription. This repression targets nuclear factor-kappaB (NF-kappaB) binding sites, revealing a key mechanism in controlling inflammation.
Area of Science:
- Molecular Biology
- Immunology
- Cell Biology
Background:
- E-selectin is crucial for leukocyte adhesion during inflammation.
- Proinflammatory stimuli like TNF-alpha and LPS induce E-selectin.
- Dexamethasone, a glucocorticoid, inhibits E-selectin expression.
Purpose of the Study:
- To elucidate the molecular mechanism of dexamethasone-mediated E-selectin repression.
- To identify the specific promoter regions and transcription factors involved.
Main Methods:
- Analysis of E-selectin promoter activity in porcine aortic endothelial cells.
- Site-directed mutagenesis to study transcription factor binding sites.
- Measurement of E-selectin mRNA and protein levels.
Main Results:
- Dexamethasone reduces E-selectin at the transcriptional level.
- The E-selectin promoter contains NF-kappaB binding sites and an NF-ELAM-1 element.
- Dexamethasone strongly represses transcription via NF-kappaB sites, but not NF-ELAM-1.
Conclusions:
- Nuclear factor-kappaB (NF-kappaB) is the primary target for dexamethasone's inhibitory effect on E-selectin expression.
- This identifies a key molecular pathway for glucocorticoid-mediated anti-inflammatory action.
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