PMID- 18849613 OWN - NLM STAT- MEDLINE DCOM- 20090309 LR - 20090216 IS - 1423-0097 (Electronic) IS - 1018-2438 (Linking) VI - 148 IP - 3 DP - 2009 TI - Immunoglobulin E-dependent regulation of the CCR3 chemokine receptor by interferon-gamma in atopic asthmatics. PG - 219-27 LID - 10.1159/000161582 [doi] AB - 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. CI - (c) 2008 S. Karger AG, Basel. FAU - Garcia-Vega, Yanelda AU - Garcia-Vega Y AD - Centro de Investigaciones Biologicas, Clinical Trials Division, La Habana, Cuba. FAU - Rodriguez-Perez, Judith AU - Rodriguez-Perez J FAU - Bermudez-Badell, Cimara AU - Bermudez-Badell C FAU - Blanco-Garces, Elizabeth AU - Blanco-Garces E FAU - Valenzuela-Silva, Carmen AU - Valenzuela-Silva C FAU - Lopez-Saura, Pedro AU - Lopez-Saura P FAU - Bello-Rivero, Iraldo AU - Bello-Rivero I LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20081010 PL - Switzerland TA - Int Arch Allergy Immunol JT - International archives of allergy and immunology JID - 9211652 RN - 0 (CCR3 protein, human) RN - 0 (Receptors, CCR3) RN - 37341-29-0 (Immunoglobulin E) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Adult MH - Asthma/blood/*drug therapy/genetics MH - Cells, Cultured MH - Double-Blind Method MH - Eosinophils/cytology/drug effects/metabolism MH - Female MH - Gene Expression Regulation/*drug effects MH - Humans MH - Immunoglobulin E/*blood MH - Interferon-gamma/*pharmacology/therapeutic use MH - Leukocyte Count MH - Leukocytes, Mononuclear/cytology/drug effects/metabolism MH - Male MH - Middle Aged MH - Neutrophils/cytology/drug effects/metabolism MH - Receptors, CCR3/*genetics MH - Treatment Outcome MH - Young Adult EDAT- 2008/10/14 09:00 MHDA- 2009/03/10 09:00 CRDT- 2008/10/14 09:00 PHST- 2007/08/06 00:00 [received] PHST- 2008/04/23 00:00 [accepted] PHST- 2008/10/14 09:00 [pubmed] PHST- 2009/03/10 09:00 [medline] PHST- 2008/10/14 09:00 [entrez] AID - 000161582 [pii] AID - 10.1159/000161582 [doi] PST - ppublish SO - Int Arch Allergy Immunol. 2009;148(3):219-27. doi: 10.1159/000161582. Epub 2008 Oct 10.