BACKGROUND: The crucial role of T helper (Th) cells and chronic inflammation in atherosclerosis and coronary artery disease is no longer controversial. Evidence has revealed that Th cell type 1 (Th1) is closely associated with the pathogenesis of acute coronary syndrome (ACS). But the mechanisms involved in the generation of Th1 cells have not been fully elucidated. IFN regulatory factor (IRF)-1 is a pleiotropic transcription factor involved in innate immunity and chronic inflammation disease. The study was undertaken to investigate the potential effect of IRF-1 on the Th1 cell function in patients with ACS in vitro. METHODS: Patients with clinical presentation of chest pain, stable angina, unstable angina, and acute myocardial infarction were enrolled in this study. Circulating CD4+ T cells were enriched and analyzed for mRNA and protein expression of IRF-1. Silencing IRF-1 gene with small interfering RNA in CD4+ T cells from patients with ACS was performed to explore the possible mechanisms involved in ACS. RESULTS: The results demonstrated that the expression of IRF-1 in CD4+ T cells was significantly increased in patients with ACS and positively correlated with plasma Th1 cytokine profile. Inhibition of IRF-1 in CD4+ T cells from patients with ACS prevented the induction of the frequencies and cytokines expression of Th1 cells. In addition, this study also revealed that IRF-1 modulate Th1 differentiation through establishing IL-12 responsiveness by acting on IL-12 receptor beta1. CONCLUSION: The present data demonstrate that inhibition of IRF-1 obviously decrease the function of Th1 cells and may be a novel participator in the progress of ACS.
BACKGROUND: The crucial role of T helper (Th) cells and chronic inflammation in atherosclerosis and coronary artery disease is no longer controversial. Evidence has revealed that Th cell type 1 (Th1) is closely associated with the pathogenesis of acute coronary syndrome (ACS). But the mechanisms involved in the generation of Th1 cells have not been fully elucidated. IFN regulatory factor (IRF)-1 is a pleiotropic transcription factor involved in innate immunity and chronic inflammation disease. The study was undertaken to investigate the potential effect of IRF-1 on the Th1 cell function in patients with ACS in vitro. METHODS:Patients with clinical presentation of chest pain, stable angina, unstable angina, and acute myocardial infarction were enrolled in this study. Circulating CD4+ T cells were enriched and analyzed for mRNA and protein expression of IRF-1. Silencing IRF-1 gene with small interfering RNA in CD4+ T cells from patients with ACS was performed to explore the possible mechanisms involved in ACS. RESULTS: The results demonstrated that the expression of IRF-1 in CD4+ T cells was significantly increased in patients with ACS and positively correlated with plasma Th1 cytokine profile. Inhibition of IRF-1 in CD4+ T cells from patients with ACS prevented the induction of the frequencies and cytokines expression of Th1 cells. In addition, this study also revealed that IRF-1 modulate Th1 differentiation through establishing IL-12 responsiveness by acting on IL-12 receptor beta1. CONCLUSION: The present data demonstrate that inhibition of IRF-1 obviously decrease the function of Th1 cells and may be a novel participator in the progress of ACS.
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Authors: K Ogasawara; S Hida; N Azimi; Y Tagaya; T Sato; T Yokochi-Fukuda; T A Waldmann; T Taniguchi; S Taki Journal: Nature Date: 1998-02-12 Impact factor: 49.962
Authors: Laura J Pinderski; Michael P Fischbein; Ganesamoorthy Subbanagounder; Michael C Fishbein; Nobuhiko Kubo; Hilde Cheroutre; Linda K Curtiss; Judith A Berliner; William A Boisvert Journal: Circ Res Date: 2002-05-31 Impact factor: 17.367
Authors: T Matsuyama; T Kimura; M Kitagawa; K Pfeffer; T Kawakami; N Watanabe; T M Kündig; R Amakawa; K Kishihara; A Wakeham Journal: Cell Date: 1993-10-08 Impact factor: 41.582
Authors: Simon Metenou; Michael Kovacs; Benoit Dembele; Yaya I Coulibaly; Amy D Klion; Thomas B Nutman Journal: Eur J Immunol Date: 2012-01-19 Impact factor: 5.532