Anti-inflammatory cytokine interleukin-19 inhibits smooth muscle cell migration and activation of cytoskeletal regulators of VSMC motility
Anti-inflammatory cytokine interleukin-19 inhibits smooth muscle cell migration and activation of cytoskeletal regulators of VSMC motility
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DOI：
10.1152/ajpcell.00439.2010
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发表时间：
2011-04-01
影响因子：
5.5
通讯作者：
Autieri, Michael V.
中科院分区：
文献类型：
--
作者：
Gabunia, Khatuna;Jain, Surbhi;Autieri, Michael V.
Gabunia K，Jain S，England RN，Autieri MV.抗炎细胞因子白细胞介素-19抑制平滑肌细胞迁移和VSMC运动的细胞骨架调节剂的激活。Am J Physiol Cell Physiol 300：C896-C906，2011.首次发表于2011年1月5日; doi：10.1152/ajpcell.00439.2010。血管平滑肌细胞（VSMC）迁移是多种血管疾病（包括动脉粥样硬化、再狭窄和移植血管病变）中的重要细胞事件。关于抗炎性白细胞介素对VSMC迁移的影响知之甚少。本研究验证了抗炎性Th 2白细胞介素，白细胞介素-19（IL-19），可以降低VSMC运动的假设。IL-19显著降低血小板衍生生长因子（PDGF）刺激的VSMC在Boyden室中的趋化性和划痕试验中的迁移。IL-19显著降低VSMC对PDGF的反应。为了确定这些细胞效应的分子机制，我们检测了IL-19对调节VSMC细胞骨架动力学和运动的蛋白质活化的影响。IL-19降低了PDGF驱动的几种细胞骨架调节蛋白的活化，这些蛋白在平滑肌细胞运动中起重要作用，包括热休克蛋白27（HSP 27）、肌球蛋白轻链（MLC）和cofilin。IL-19降低了PDGF对Rac 1和RhoA GTP酶（迁移信号的重要整合子）的激活。IL-19不能抑制VSMC迁移，也不能抑制VSMC中细胞骨架调节蛋白的激活，转导有组成性活性的Rac 1突变体（RacV 14），这表明IL-19抑制Rac 1激活附近的事件。总之，这些数据首次表明IL-19对VSMC运动和细胞骨架调节蛋白的活化具有重要的抑制作用。这对于使用抗炎细胞因子治疗血管闭塞性疾病具有重要意义。
Gabunia K, Jain S, England RN, Autieri MV. Anti-inflammatory cytokine interleukin-19 inhibits smooth muscle cell migration and activation of cytoskeletal regulators of VSMC motility. Am J Physiol Cell Physiol 300: C896-C906, 2011. First published January 5, 2011; doi:10.1152/ajpcell.00439.2010.-Vascular smooth muscle cell (VSMC) migration is an important cellular event in multiple vascular diseases, including atherosclerosis, restenosis, and transplant vasculopathy. Little is known regarding the effects of anti-inflammatory interleukins on VSMC migration. This study tested the hypothesis that an anti-inflammatory Th2 interleukin, interleukin-19 (IL-19), could decrease VSMC motility. IL-19 significantly decreased platelet-derived growth factor (PDGF)-stimulated VSMC chemotaxis in Boyden chambers and migration in scratch wound assays. IL-19 significantly decreased VSMC spreading in response to PDGF. To determine the molecular mechanism(s) for these cellular effects, we examined the effect of IL-19 on activation of proteins that regulate VSMC cytoskeletal dynamics and locomotion. IL-19 decreased PDGF-driven activation of several cytoskeletal regulatory proteins that play an important role in smooth muscle cell motility, including heat shock protein-27 (HSP27), myosin light chain (MLC), and cofilin. IL-19 decreased PDGF activation of the Rac1 and RhoA GTPases, important integrators of migratory signals. IL-19 was unable to inhibit VSMC migration nor was able to inhibit activation of cytoskeletal regulatory proteins in VSMC transduced with a constitutively active Rac1 mutant (RacV14), suggesting that IL-19 inhibits events proximal to Rac1 activation. Together, these data are the first to indicate that IL-19 can have important inhibitory effects on VSMC motility and activation of cytoskeletal regulatory proteins. This has important implications for the use of anti-inflammatory cytokines in the treatment of vascular occlusive disease.