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Low-dose theophylline restores corticosteroid responsiveness in rats with smoke-induced airway inflammation
- Source :
- Canadian Journal of Physiology and Pharmacology. 90:895-902
- Publication Year :
- 2012
- Publisher :
- Canadian Science Publishing, 2012.
-
Abstract
- Patients with chronic obstructive pulmonary disease (COPD) respond poorly to corticosteroids. Histone deacetylase-2 (HDAC-2) plays a pivotal role in many cases of steroid insensitivity. The main aim of this study was to restore the smoking-induced reduction in corticosteroid sensitivity by increasing HDAC-2 activity using low-dose theophylline. Rats were exposed to cigarette smoke (CS) and treated with budesonide and two doses of theophylline. Besides the pathologic examination and cell counting in the bronchoalveolar lavage fluid (BALF), the expression of HDAC-2 and CXC chemokine ligand-8 (CXCL-8) were measured. Airway inflammation induced by CS was demonstrated by pathologic changes of lung tissue and increased level of CXCL-8. CS exposure also markedly decreased HDAC-2 expression. Moreover, a negative correlation was found between HDAC-2 activity and a lung destruction index. The index was restored to control levels with inhaled corticosteroid treatment in combination with a low, not a high, dose of theophylline. These results indicate that low-dose theophylline might provide protection from smoke damage and improve the anti-inflammatory effects of steroids by increasing HDAC-2 activity.
- Subjects :
- Male
medicine.medical_specialty
Physiology
medicine.drug_class
medicine.medical_treatment
Histone Deacetylase 2
Steroid
Theophylline
Adrenal Cortex Hormones
Smoke
Physiology (medical)
Internal medicine
medicine
Animals
Rats, Wistar
Budesonide
Lung
Inflammation
Pharmacology
COPD
Dose-Response Relationship, Drug
biology
Histone deacetylase 2
Chemistry
Interleukin-8
Smoking
Airway inflammation
General Medicine
Smoke Inhalation Injury
medicine.disease
Rats
Histone
Endocrinology
biology.protein
Corticosteroid
Bronchoalveolar Lavage Fluid
medicine.drug
Subjects
Details
- ISSN :
- 12057541 and 00084212
- Volume :
- 90
- Database :
- OpenAIRE
- Journal :
- Canadian Journal of Physiology and Pharmacology
- Accession number :
- edsair.doi.dedup.....58aca9d2451e4ea3aa21d0a5ddc74b70