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Induction and Analysis of Oxidative Stress in Sleeping Beauty Transposon-Transfected Human Retinal Pigment Epithelial Cells
Published on: December 11, 2020
Oxidative stress modulates theophylline effects on steroid responsiveness
John A Marwick1, Gillian Wallis, Koremu Meja
1National Heart & Lung Institute, Airways Disease Section, Imperial College London, Guy-Scadding Building, Dovehouse Steet, London SW3 6LY, UK. j.marwick@imperial.ac.uk
Biochemical and Biophysical Research Communications
|October 28, 2008
Summary
Low concentrations of theophylline restore corticosteroid anti-inflammatory action in cells experiencing oxidative stress. This occurs by altering theophylline
Area of Science:
- Immunology and Pharmacology
- Cellular Biology
Background:
- Oxidative stress is implicated in chronic inflammatory diseases like asthma and COPD.
- It diminishes the effectiveness of anti-inflammatory corticosteroids, contributing to treatment resistance.
Purpose of the Study:
- To investigate the mechanism by which low-dose theophylline restores corticosteroid function in cells under oxidative stress.
- To analyze the effects of theophylline on gene expression and protein interactions in both normal and oxidant-exposed cells.
Main Methods:
- Utilized cell cultures exposed to oxidants.
- Administered low concentrations of theophylline.
- Performed global gene expression analysis.
- Conducted quantitative chemoproteomics to identify theophylline's binding targets.
Main Results:
- Theophylline restored corticosteroid repression of pro-inflammatory mediators and histone acetylation in oxidant-exposed cells.
- Gene expression analysis revealed distinct pathways regulated by theophylline in naive versus oxidant-exposed cells.
- Quantitative chemoproteomics showed that oxidative stress alters theophylline's binding affinity and targets.
Conclusions:
- Oxidative stress modifies theophylline's binding profile and gene expression patterns.
- These alterations may underlie theophylline's ability to restore corticosteroid function in inflammatory conditions.
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