Global expression profiling of theophylline response genes in macrophages: Evidence of airway anti-inflammatory regulation
Journal
Respiratory Research
Journal Volume
6
Pages
89
Date Issued
2005
Author(s)
Abstract
Background: Theophylline has been used widely as a bronchodilator for the treatment of bronchial asthma and has been suggested to modulate immune response. While the importance of macrophages in asthma has been reappraised and emphasized, their significance has not been well investigated. We conducted a genome-wide profiling of the gene expressions of macrophages in response to theophylline. Methods: Microarray technology was used to profile the gene expression patterns of macrophages modulated by theophylline. Northern blot and real-time quantitative RT-PCR were also used to validate the microarray data, while Western blot and ELISA were used to measure the levels of IL-13 and LTC4. Results: We identified dozens of genes in macrophages that were dose-dependently down- or upregulated by theophylline. These included genes related to inflammation, cytokines, signaling transduction, cell adhesion and motility, cell cycle regulators, and metabolism. We observed that IL-13, a central mediator of airway inflammation, was dramatically suppressed by theophylline. Real-time quantitative RT-PCR and ELISA analyses also confirmed these results, without respect to PMA-treated THP-1 cells or isolated human alveolar macrophages. Theophylline, rolipram, etazolate, db-cAMP and forskolin suppressed both IL-13 mRNA expression (?25%, 2.73%, 8.12%, 5.28%, and 18.41%, respectively) and protein secretion (<10% production) in macrophages. These agents also effectively suppressed LTC4 expression. Conclusion: Our results suggest that the suppression of IL-13 by theophylline may be through cAMP mediation and may decrease LTC4 production. This study supports the role of theophylline as a signal regulator of inflammation, and that down regulation of IL-13 by theophylline may have beneficial effects in inflammatory airway diseases. ? 2005 Yao et al; licensee BioMed Central Ltd.
SDGs
Other Subjects
bucladesine; cyclic AMP; etazolate; forskolin; interleukin 13; leukotriene C4; messenger RNA; rolipram; theophylline; antiinflammatory agent; immunologic factor; interleukin 13; leukotriene C4; proteome; theophylline; antiinflammatory activity; article; cell adhesion; cell cycle; cell isolation; cell metabolism; cell motility; controlled study; cytokine production; cytokine release; DNA microarray; DNA responsive element; dose response; down regulation; drug response; enzyme linked immunosorbent assay; gene expression; gene expression profiling; gene function; gene identification; human; human cell; immunomodulation; immunosuppressive treatment; inflammation; macrophage; Northern blotting; respiratory tract inflammation; reverse transcription polymerase chain reaction; signal transduction; validation process; Western blotting; bronchitis; cell line; drug effects; gene expression regulation; lung alveolus; macrophage activation; metabolism; pathology; Anti-Inflammatory Agents; Bronchitis; Cell Line; Dose-Response Relationship, Drug; Gene Expression Profiling; Gene Expression Regulation; Humans; Immunologic Factors; Interleukin-13; Leukotriene C4; Macrophage Activation; Macrophages; Proteome; Pulmonary Alveoli; Theophylline
Type
journal article