T-bet/GATA-3 ratio as a measure of the Th1/Th2 cytokine profile and novel targets of CpG ODN intervention in asthma patients / 中国病理生理杂志

ABSTRACT

AIM:The aim of this study is to investigate the relationship between the ratio of transcription factors T-bet/GATA-3 in peripheral blood mononuclear cells(PBMCs)and the imbalance of Th1/Th2 cytokines from patients with asthma,and to examine whether and how CpG ODN intervention would restore the imbalanced Th1/Th2 profile in asthma patients.METHODS:Three groups of subjects with asthma(asthma group),chronic obstructive pulmonary disease(COPD group),and normal controls(control group)were included in this study.T-bet,GATA-3 and TLR9 mRNA levels were measured by reverse transcription-polymerase chain reaction(RT-PCR).Th1 cytokine IFN-? and Th2 cytokines IL-4,IL-5 and IL-13 were measured by enzyme-linked immunoabsorbent assay(ELISA)in asthma group.Cultured PBMCs from asthma patients with CpG ODN incubation were collected for measuring T-bet,GATA-3 mRNA and TLR9 mRNA.RESULTS:The ratio of T-bet/GATA-3 in asthma group was significantly lower than that in the COPD group and control group.The serum levels of IL-4,IL-5 and IL-13 had positive correlation with the ratio of T-bet/GATA-3 in asthmatic patients,and the lower serum level of IFN-? had negative correlation with the ratio.The TLR9 mRNA expression in asthma was significantly attenuated than that in COPD group and control group.Consequently,the ratio of T-bet/GATA-3 in CpG group was significantly enhanced than that in control group.CONCLUSION:These results indicate that the ratio of T-bet/GATA-3 in asthma is decreased and could represent the imbalance of Th1/Th2 cells.CpG ODN influences the ratio of T-bet/GATA-3,upregulating the T-bet mRNA expression and downregulating the GATA-3 mRNA expression,which is able to reverse the imbalance of Th1/Th2 cells.CpG-ODN may be a promising therapeutic target for asthma.