Abstract | BACKGROUND: The chemokine receptor CCR3 mediates the migration of cells that play an important role in the pathogenesis of asthma to inflammatory foci. Interferon (IFN)-gamma is known to downregulate the expression of some chemokine receptors. Therefore, we decided to analyze the regulation of CCR3 by IFN-gamma in asthmatics and to characterize the dependence of this process on immunoglobulin E ( IgE) levels. METHODS: Atopic asthmatics were treated with IFN-gamma or placebo, and the IgE concentration in the blood was measured using an ultra-micro-ELISA for total IgE. Mononuclear cells from patients and controls were isolated by Ficoll- Hypaque gradient and incubated in the absence or presence of IFN-gamma for different periods of time. After incubation, the cells were washed and lysed for RT-PCR analysis, which was performed using a Perkin-Elmer kit. RESULTS: IFN-gamma treatment apparently improved the evaluated clinical variables; however, the differences were not significant compared to the placebo group. We found that IFN-gamma downregulated CCR3 mRNA expression ex vivo and in vivo in those patients with IgE levels higher than 500 IU/ml, whereas IFN-gamma upregulated CCR3 mRNA expression in patients with IgE levels lower than 500 IU/ml. Correspondence between ex vivo and in vivo results was observed using this approach. There was found to be a direct correlation between total serum IgE and CCR3 mRNA expression. CONCLUSIONS: In those asthmatic patients with high levels of IgE, who are thus susceptible to downregulation of CCR3 by IFN- gamma, a significant therapeutic effect with systemic IFN-gamma might be expected.
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Authors | Yanelda García-Vega, Judith Rodríguez-Perez, Cimara Bermúdez-Badell, Elizabeth Blanco-Garcés, Carmen Valenzuela-Silva, Pedro López-Saura, Iraldo Bello-Rivero |
Journal | International archives of allergy and immunology
(Int Arch Allergy Immunol)
Vol. 148
Issue 3
Pg. 219-27
( 2009)
ISSN: 1423-0097 [Electronic] Switzerland |
PMID | 18849613
(Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Copyright | (c) 2008 S. Karger AG, Basel. |
Chemical References |
- CCR3 protein, human
- Receptors, CCR3
- Immunoglobulin E
- Interferon-gamma
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Topics |
- Adult
- Asthma
(blood, drug therapy, genetics)
- Cells, Cultured
- Double-Blind Method
- Eosinophils
(cytology, drug effects, metabolism)
- Female
- Gene Expression Regulation
(drug effects)
- Humans
- Immunoglobulin E
(blood)
- Interferon-gamma
(pharmacology, therapeutic use)
- Leukocyte Count
- Leukocytes, Mononuclear
(cytology, drug effects, metabolism)
- Male
- Middle Aged
- Neutrophils
(cytology, drug effects, metabolism)
- Receptors, CCR3
(genetics)
- Treatment Outcome
- Young Adult
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