[冠心病患者外周血单核细胞的促炎细胞因子和信号通路]。

A. V. Logatkina, V. S. Nikiforov, S. Bondar, I. Terekhov
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引用次数: 5

摘要

目的探讨冠心病(CHD)患者外周血单核细胞(MNC)的含量及其功能状态和细胞因子产生的相关因素。材料与方法采用免疫酶法测定MNC裂解液中蛋白激酶JNK1/2、ERK1/2、MAPK38、AKT1、JAK2、FAK、AMPK、p70S6K、STAT3、STAT5B、STAT6的浓度。测定血清白细胞介素1β、2、4和y-干扰素水平。结果用力型心绞痛和不稳定型心绞痛患者JNK水平分别比正常患者高59.8% (p < 0.05)和53.1% (p < 0.05)。核转录因子水平分别为26.9%(0.015)和27.9% (0.017),JAK2 31.5%(0.022)和48.6% (0.018),STAT3 49.6%(0.025)和55.3% (0.02),STAT5B 21.5%(0.018)和30.2%(0.011)。这些变化与STAT6水平上升13.1%(0.047)和51.4%(0.019)、FAK水平上升30.1%(0.025)和79.4%(0.03)、7.6%(0.09)和15.2% (0.039)АКТ1水平、65.3(0.02)和76.2% (0.017)p70S6K水平升高相关。结论研究结果表明,冠心病患者全血细胞持续的促炎激活是由于MNC中MAPK/SAPK信号通路成分IL-1和IL-2水平的升高以及决定细胞对IL-10敏感性的STAT3水平的降低。细胞内ERK和JNK水平的升高是MNC对促炎细胞因子的高反应性的原因。
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[PROINFLAMMATORY CYTOKINES AND SIGNALING PATHWAYS IN PERIPHERAL BLOOD MONONUCLEAR CELLS IN PATIENTS WITH CORONARY ARTERY DISEASE].
Aim To determine content of mononuclear ells (MNC) in peripheral blood of patients with coronary heart disease (CHD) and factors responsible for their functional state and cytokine production. Materials and methods Concentration of proteinkinases JNK1/2, ERK1/2, MAPK38, AKT1, JAK2, FAK, AMPK, p70S6K, STAT3, STAT5B and STAT6 was determined in MNC lysate by immune-enzyme assay. Interleukin 1β, 2, 4 and y-interferon levels were measured in blood sera. Results In patients with angina of effort and unstable angina, the JNK level was 59,8% and 53,1% higher than the normal one respectively (р=0,013) and (р=0,012). The level of the nuclear transcription factor was 26,9% (р=0,015) and 27,9% (р=0,017), JAK2 31,5% (р=0,022) and 48,6% (р=0,018), STAT3 49,6% (р=0,025) and 55,3% (р=0,02), STAT5B 21,5% (р=0,018) and 30,2% (р=0,011) lower. These changes were associated with a 13,1% (р=0,047) and 51,4% (р=0,019) rise in the STAT6 level, 30,1% (р=0,025) and 79,4% (р=0,003) FAK level, 7,6% (р=0,09) and 15,2% (р=0,039) АКТ1 level, 65,3 (р=0,02) and 76,2% (р=0,017) p70S6K level. Conclusion Results of the study suggest persistent pro-inflammatory activation of whole blood cells in CHD patients due to enhanced levels of IL-1 and IL-2, components of the MAPK/SAPK signal pathway in MNC and decreased STAT3 level determining cell sensitivity to IL-10. The elevated intracellular level of ERK and JNK us responsible for high responsiveness of MNC to pro-inflammatory cytokines.
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