Immunoglobulin E-dependent regulation of the CCR3 chemokine receptor by interferon-gamma in atopic asthmatics.
Int Arch Allergy Immunol
; 148(3): 219-27, 2009.
Article
en En
| MEDLINE
| ID: mdl-18849613
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Asma
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Inmunoglobulina E
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Regulación de la Expresión Génica
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Interferón gamma
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Receptores CCR3
Tipo de estudio:
Clinical_trials
Límite:
Adult
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Int Arch Allergy Immunol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2009
Tipo del documento:
Article
País de afiliación:
Cuba
Pais de publicación:
Suiza