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Glucocorticoids regulate glutamine synthetase expression in lung epithelial cells
S F Abcouwer1, G C Lukaszewicz, W W Souba
1Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
The American Journal of Physiology
|January 1, 1996
Summary
Glucocorticoids like dexamethasone increase lung glutamine synthetase (GS) expression during sepsis. This response is mediated by the glucocorticoid receptor and affects GS mRNA stability.
Area of Science:
- Pulmonary medicine
- Molecular biology
- Biochemistry
Background:
- During sepsis, lung glutamine efflux increases, supported by elevated glutamine synthetase (GS) activity.
- Understanding the regulation of GS in lung epithelial cells is crucial for managing septic states.
Purpose of the Study:
- To investigate the effects of hormones and cytokines on glutamine synthetase (GS) expression in rat lung epithelial cells (L2).
- To elucidate the role of glucocorticoids in regulating GS expression and mRNA stability.
Main Methods:
- Utilized an L2 cell culture model to study GS expression.
- Administered dexamethasone (Dex), lipopolysaccharide (LPS), cytokines, C5a, and prostaglandins.
- Assessed GS mRNA and protein levels, and mRNA decay kinetics using actinomycin D and cycloheximide (CHX).
Main Results:
- Dexamethasone (Dex) significantly increased GS mRNA and protein levels in L2 cells.
- LPS, cytokines, C5a, and prostaglandins did not markedly induce GS expression.
- Dex-induced GS mRNA increase was blocked by RU-38486 and actinomycin D, but not CHX.
- CHX and actinomycin D modulated GS mRNA half-life, influencing superinduction and decay.
Conclusions:
- Lung GS expression is primarily regulated by a direct glucocorticoid receptor-mediated mechanism.
- GS mRNA decay in L2 cells is controlled by at least two independent pathways sensitive to CHX and actinomycin D.