In vitro interferon gamma regulation of CCR-3 mRNA expression in peripheral blood leukocytes from atopic asthmatics.
Interferon gamma (IFN-gamma) exerts major pro-inflammatory, regulatory, and anti-inflammatory actions in immune defense responses. In asthma the infiltration of eosinophils, neutrophils, and lymphocytes is a critical event. Chemokines stimulate the migration of the susceptible subset of inflammatory cells. The chemokine receptors CCR-3 are mainly expressed in eosinophils, basophils, and Th2 cells. More recently it has been demonstrated that the IFN-gamma downregulates the expression of some chemokine receptors. IgE determinations were performed using an ELISA for total IgE Peripheral blood leukocytes from patients and controls were isolated by Ficoll-Hypaque gradient. The cells were incubated in the absence or presence of 500 IU/ml of recombinant human IFN-gamma for different times. After incubation the cells were washed and lyzed for reverse transcription-polymerase chain reaction (RT-PCR) analysis. RT-PCR was performed using a Perkin-Elmer kit. The amplified bands were run in 2% agarose gels and quantified. The basal levels of CCR-3 in asthmatic patients with IgE > 150 IU/ml tend to be higher than in controls. IFN-gamma down-regulates the expression of CCR-3 in peripheral blood leukocytes from asthmatics with IgE >150 IU/ml, when compared with the basal levels of expression. In conclusions, through the modification of the expression of CCR-3 in peripheral blood leukocytes from atopic asthmatics, IFN-gamma could exert a beneficial effect in patients with asthma, regulating the migration of some inflammatory cells involved in the pathogenesis of the disease.
Bello
I
I
Centro de Investigaciones Biológicas, Clinical Trials Division, La Habana, Cuba. iraldo.bello@cigb.edu.cu
Rizo
M R
MR
Badel
C B
CB
Blanco
E
E
Valenzuela
C
C
del Rosario
M
M
Quiroga
M R
MR
Bayard
R B
RB
Saldivar
J C
JC
Lopez-Saura
P
P
D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000188:drug therapy / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology* / Q000627:therapeutic use; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis*; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
C515350:CCR3 protein, human; D012333:RNA, Messenger; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D007371:Interferon-gamma