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Dexamethasone increases αvβ3 integrin expression and affinity through a calcineurin/NFAT pathway
Jennifer A Faralli1, Debjani Gagen1, Mark S Filla2
1Department of Pathology & Laboratory Medicine, University of Wisconsin, Madison, WI 53706, USA.
Biochimica Et Biophysica Acta
|October 9, 2013
Summary
Dexamethasone (DEX) treatment increases αvβ3 integrin expression by upregulating the β3 subunit. This effect is a secondary glucocorticoid response mediated by the calcineurin/NFAT pathway and persists after DEX removal.
Area of Science:
- Cell Biology
- Molecular Biology
- Immunology
Background:
- Integrins are crucial cell surface receptors involved in cell adhesion and signaling.
- Glucocorticoids, like dexamethasone (DEX), are potent anti-inflammatory agents with diverse cellular effects.
- The αvβ3 integrin plays a role in various physiological and pathological processes, including inflammation and angiogenesis.
Purpose of the Study:
- To investigate the regulatory mechanisms by which dexamethasone (DEX) influences the expression and activity of the αvβ3 integrin.
- To elucidate the specific integrin subunits affected by DEX treatment.
- To identify the signaling pathways involved in DEX-mediated αvβ3 integrin regulation.
Main Methods:
- Flow cytometry (FACS) was used to analyze αvβ3 integrin expression and activation.
- Quantitative real-time PCR (qPCR) was employed to measure β3 and β1 integrin mRNA levels.
- Inhibition studies using RU486, cycloheximide, cyclosporin A (CsA), and FK506 were conducted to probe the underlying molecular mechanisms.
Main Results:
- DEX treatment induced a significant upregulation of αvβ3 integrin, characterized by increased expression of the β3 integrin subunit.
- β3 integrin mRNA levels were elevated by DEX in a time-dependent manner and remained high even after DEX withdrawal.
- DEX-induced β3 integrin mRNA upregulation was partly due to increased mRNA half-life and required de novo protein synthesis of an activation factor, involving the calcineurin/NFAT pathway.
Conclusions:
- Dexamethasone treatment leads to a sustained increase in αvβ3 integrin expression, primarily through the upregulation of the β3 integrin subunit.
- This DEX-induced effect is a secondary glucocorticoid response mediated by the calcineurin/NFAT signaling pathway.
- The findings suggest a novel mechanism by which glucocorticoids modulate integrin function, potentially impacting inflammatory and immune responses.
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