Kazanski V, Mitrokhin V M, Mladenov M I, Kamkin A G
a Department of Fundamental and Applied Physiology , Russian National Research Medical University , Moscow , Russia.
b Faculty of Natural Sciences and Mathematics, Institute of Biology , "Ss. Cyril and Methodius" University , Skopje , Macedonia.
Immunol Invest. 2017 Jan;46(1):22-37. doi: 10.1080/08820139.2016.1208220. Epub 2016 Sep 12.
The role of cytokines as regulators of stretch-related mechanisms is of special importance since mechano-sensitivity plays an important role in a wide variety of biological processes. Here, we elucidate the influence of cytokine application on mechano-sensitivity and mechano-transduction. The atrial myocardial stretch induces production of interleukin (IL)-2, IL-6, IL-13, IL-17A, and IL-18 with exception of tumor necrosis factor α (TNF-α), IL-1β, and vascular endothelial growth factor B (VEGF-B). Positive ionotropic effect was specific for VEGF-B, negative ionotropic effects were specific for TNF-α, IL-1β, IL-2, IL-6, IL-13, IL-17A and IL-18, while IL-1α doesn't show direct ionotropic effect. The IL-2, IL-6, IL-17A, IL-18, and VEGF-B cause elongation of the APD, in comparison with the reduced APD caused by the IL-13. The TNF-α, IL-1β, and IL-18 influences L-type Ca channels, IL-2 has an inhibitory effect on the fast Na channels while IL-17A and VEGF-B were specific for Kir channels. With exception of the IL-1α, IL-2, and VEGF-B, all analyzed cytokines include nitric oxide dependent signaling with resultant combined effects on mechano-gated and Ca channels. The relationships between these pathways and the time-dependence of their activation are of important considerations in the evaluation of cytokine-induced electrical abnormality, specific for cardiac dysfunctions. In general, the discussion presented in this review covers research devoted to counterbalance between different cytokines in the regulation of stretch-induced effects in rat atrial myocardium.
APs: action potentials; APD25: action potential durations to 25% of re-polarization; APD50: action potential durations to 50% of repolarization; APD90: action potential durations to 90% of repolarization; MGCs: mechanically gated channels.
细胞因子作为牵张相关机制的调节因子具有特殊重要性，因为机械敏感性在多种生物学过程中发挥重要作用。在此，我们阐明细胞因子应用对机械敏感性和机械转导的影响。心房心肌牵张可诱导白细胞介素（IL）-2、IL-6、IL-13、IL-17A和IL-18的产生，但肿瘤坏死因子α（TNF-α）、IL-1β和血管内皮生长因子B（VEGF-B）除外。正性变力作用对VEGF-B具有特异性，负性变力作用对TNF-α、IL-1β、IL-2、IL-6、IL-13、IL-17A和IL-18具有特异性，而IL-1α未表现出直接的变力作用。与IL-13导致的动作电位时程（APD）缩短相比，IL-2、IL-6、IL-17A、IL-18和VEGF-B可使APD延长。TNF-α、IL-1β和IL-18影响L型钙通道，IL-2对快速钠通道具有抑制作用，而IL-17A和VEGF-B对钾离子通道（Kir通道）具有特异性。除IL-1α、IL-2和VEGF-B外，所有分析的细胞因子均包括一氧化氮依赖性信号传导，对机械门控通道和钙通道产生综合作用。在评估细胞因子诱导的电异常（这对心脏功能障碍具有特异性）时，这些途径之间的关系及其激活的时间依赖性是重要的考虑因素。总体而言，本综述中的讨论涵盖了致力于研究大鼠心房心肌中不同细胞因子在调节牵张诱导效应时的平衡的研究。
APs：动作电位；APD25：复极化至25%时的动作电位时程；APD50：复极化至50%时的动作电位时程；APD90：复极化至90%时的动作电位时程；MGCs：机械门控通道
