The Effect And Mechanism Of IFN Regulatory Factor-1 On T Helper Lymphocyte Differentiation In Patients With Acute Coronary Syndrome

Aim:IFN regulatory factor (IRF)-1 is a pleiotropic transcription factor involved in autoimmune disease. The aim of the study was to investigate the expression of IRF-1 in CD4+ T cells and explore the possible role of IRF-1 in AS and ACS.Methods:Patients with clinical presentation of chest pain (CPS), stable angina (SA), unstable angina (UA) and acute myocardial infarction (AMI) were enrolled in this study. CD4+ T cells were enriched and analyzed for the expression of IRF-1. The concentrations of plasma Thl cytokines IFN-γ,TNF-α,IL-12 and Treg related cytokines TGF-(31 and IL-10 were detected by ELISA. The correlation between IRF-1 and cytokines were analyzed by Pearson correlation analysis.Results:The results demonstrated that the expression of IRF-1 in CD4+T cells was significantly increased in patients with ACS. The expression of IRF-1 were positively correlated with plasma Thl cytokines and negatively correlated with plasma Treg related cytokines.Conclusion:The present data demonstrate that the up-regulation of IRF-1 may be one of the mechanisms in the onset of ACS. It may play a potential role in the differentiation of Th cells in ACS and may be a novel therapeutic target for ACS. Aim:The crucial role of Th cells in atherosclerosis in no longer controversial. The aim of the study was to investigate the effect of IRF-1siRNA in the differentiation of Thl and CD4+CD25+Treg.Methods:4 pairs of sense and antisense RNA oligonucleotide strands targeted to human IRF-1 and 1 pair of unrelated siRNA were designed and synthesized. Then the plasmids were transfected into cultured CD4+ T cells in patients with ACS using lipofectamine2000. Screen out the most potent plasmid recombinant by the means of Real-time PCR (RT-PCR) and Western Blotting. CD4+ T cells in patients with ACS were then divided into three groups: ACS group; IRF-1 siRNA group; unrelated siRNA group which transfected with IRF-siRNA or unrelated siRNA. Lastly, the function of Thl and CD4+CD25+ Treg were analyzed to explore the effect of IRF-1 on the differentiation of Th cells.Results:After administrated with IRF-1 siRNA, the frequency of Thl and the expression of Thl cytokines were significantly decreased. In contrast, the frequency and the function of CD4+CD25+Treg improved obviously.Conclusion:The present data demonstrate that inhibition of IRF-1 could prevent the induction of the function of Thl, but elevated the function of CD4+CD25+Treg. It may modulate the differentiation of Th cells and participate in the process of inflammation of ACS. Aim:IRF-1 is an important transcription factor involved in immunity and interacts with many other transcription factors. The aim of the study was to investigate the possible mechanism of IRF-1 in the differentiation of Thl and CD4+CD25+ Treg.Methods:CD4+T cells in 12 patients with ACS were divided into three groups:ACS group; IRF-1 siRNA group; unrelated siRNA group which transfected with IRF-siRNA or unrelated siRNA. The mRNA and protein levels of IL-12Rβ1,T-bet and Foxp3 by the means of Real-time PCR and western blot.Results:After administrated with IRF-1 siRNA, the transcription and protein level of IL-12Rβ1,T-bet were significantly decreased. In contrast, the transcription and protein level of Foxp3 improved obviously.Conclusion:The present data demonstrate that inhibition of IRF-1 could modulate IL-12 pathway and Foxp3 pathways, which further modulate the function of Th1 and CD4+CD25+Treg and then play potential role in the inflammation of ACS.