The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index.
A molecular mechanism of action of theophylline: Induction of histone deacetylase activity to decrease inflammatory gene expression
Open accessAbstract
The molecular mechanism for the anti-inflammatory action of theophylline is currently unknown, but low-dose theophylline is an effective add-on therapy to corticosteroids in controlling asthma. Corticosteroids act, at least in part, by recruitment of histone deacetylases (HDACs) to the site of active inflammatory gene transcription. They thereby inhibit the acetylation of core histones that is necessary for inflammatory gene transcription. We show both in vitro and in vivo that low-dose theophylline enhances HDAC activity in epithelial cells and macrophages. This increased HDAC activity is then available for corticosteroid recruitment and predicts a cooperative interaction between corticosteroids and theophylline. This mechanism occurs at therapeutic concentrations of theophylline and is dissociated from phosphodiesterase inhibition (the mechanism of bronchodilation) or the blockade of adenosine receptors, which are partially responsible for its side effects. Thus we have shown that low-dose theophylline exerts an anti-asthma effect through increasing activation of HDAC which is subsequently recruited by corticosteroids to suppress inflammatory genes.
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Self-citationInflammatory Mediators of Asthma: An Update
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Self-citationAnti-inflammatory effects of low-dose oral theophylline in atopic asthma
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Self-citationImmunomodulation by theophylline in asthma. Demonstration by withdrawal of therapy.
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Barnes, P. J., Shapiro, S. D., & Pauwels, R. A. (2003) · European Respiratory Journal · doi:10.1183/09031936.03.00040703 · Cited by 1,439
Self-citationRegulation of inflammation and redox signaling by dietary polyphenols
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Pharmacokinetics and pharmacodynamics of systemically administered glucocorticoids.
Czock, D., Keller, F., Rasche, F. M., & H??ussler, U. (2005) · Clinical Pharmacokinetics · doi:10.2165/00003088-200544010-00003 · Cited by 886
Interindividual Differences in Caffeine Metabolism and Factors Driving Caffeine Consumption
Nehlig, A. (2018) · Pharmacological Reviews · doi:10.1124/pr.117.014407 · Cited by 632
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Metadata
- Authors
- Ito, K., Lim, S., Caramori, G., Cosio, B., Chung, K. F., Adcock, I. M., & Barnes, P. J.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2002-06-17
- Volume
- 99
- Issue
- 13
- Pages
- 8921-8926
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2013407710
- Cited by
- 512
- References
- 23
- FWCI
- 7.45
- Type
- journal article
- Language
- en
- Open access
- green
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- Ito, K., Lim, S., Caramori, G., Cosio, B., Chung, K. F., Adcock, I. M., & Barnes, P. J. (2002). A molecular mechanism of action of theophylline: Induction of histone deacetylase activity to decrease inflammatory gene expression. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.132556899
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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