Inhibiting nonmuscle myosin II impedes inflammatory infiltration and ameliorates progressive renal disease
Inhibiting nonmuscle myosin II impedes inflammatory infiltration and ameliorates progressive renal disease
复制标题
抑制非肌肉肌球蛋白 II 可阻止炎症浸润并改善进行性肾病
作者：
Jin Si;Y. Ge;S. Zhuang;R. Gong
运动蛋白非肌肉肌球蛋白II（nonmuscle myosin II，NMII）通过与肌动蛋白细胞骨架的相互作用构成细胞爬行的机制，在炎症反应和免疫反应中驱动免疫活性细胞的运动和浸润中发挥重要作用。Blebbistatin是一种高度选择性的NMII腺苷三磷酸酶抑制剂。本研究检测了blebbistatin抑制NMII对炎症的影响。在体外，blebbistatin显着诱导放线菌球蛋白复合物解体在各种培养的免疫细胞，功能受损的运动活性和侵袭能力的评估Boyden室运动试验和matrigel侵袭试验。在体内，在由肿瘤坏死因子诱导的急性炎症大鼠模型中，blebbistatin以剂量依赖性方式消除循环荧光标记的巨噬细胞的肾隔离。此外，在进行性梗阻性肾病大鼠中，blebbistatin治疗表现出显著的肾脏保护作用，如肾脏重量正常化、大体形态改善和肾小管组织学损伤减少所证明。这种有益作用与肾脏炎症的显著改善相关，与blebbistatin的主要抗炎作用一致。此外，在已建立阻塞性肾病的大鼠中，blebbistatin预处理的巨噬细胞显示出向发炎的肾实质中的清除性募集，表明blebbistatin直接阻碍免疫细胞的炎症浸润。总的来说，我们的研究结果表明，抑制NMII有一个强大的和直接的抗炎作用的基础上的损伤的放线菌球蛋白动力机车机械，这是必不可少的迁移和浸润的免疫活性细胞。
The motor protein nonmuscle myosin II (NMII) through its interaction with the actin cytoskeleton constitutes the machinery of cell crawling and has an important role in driving locomotion and infiltration of immune competent cells during inflammatory response and immune reaction. Blebbistatin is a highly selective inhibitor of NMII adenosine triphosphatase. This study examined the effect of NMII inhibition by blebbistatin on inflammation. In vitro, blebbistatin markedly induced actinomyosin complex disassembly in various cultured immunocytes, and functionally impaired their motile activity and invasive capacity as assessed by the Boyden chamber motility assay and the matrigel invasion assay. In vivo, in a rat model of acute inflammation induced by tumor necrosis factor, blebbistatin obliterated renal sequestration of circulating fluorescence-labeled macrophages in a dose-dependent fashion. Moreover, in rats with progressive obstructive nephropathy, blebbistatin treatment exhibited a remarkable renoprotective effect, as evidenced by normalized kidney weight, improved gross morphology, and diminished histologic injury in the tubulointerstitium. This beneficial effect was associated with significant amelioration of renal inflammation, consistent with a primary anti-inflammatory action by blebbistatin. In addition, in rats with established obstructive nephropathy, blebbistatin pretreated macrophages showed obliterated recruitment into the inflamed renal parenchyma, denoting that blebbistatin directly impedes inflammatory infiltration by immunocytes. Collectively, our findings suggest that inhibition of NMII has a potent and direct anti-inflammatory effect on the basis of impairment of the actinomyosin powered locomotive machinery, which is essential for migration and infiltration of immune competent cells.
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影响因子：
4
作者：
Robert J. Eddy;L. Pierini;Fumio Matsumura;Frederick R. Maxfield
通讯作者：
Robert J. Eddy;L. Pierini;Fumio Matsumura;Frederick R. Maxfield
DOI：
10.1097/01.asn.0000095249.99803.85
发表时间：
2003-11-01
影响因子：
13.6
作者：
Haroun, MK;Jaar, BG;Coresh, J
通讯作者：
Coresh, J
影响因子：
13.6
作者：
Gong, Rujun;Rifai, Abdalla;Dworkin, Lance D.
通讯作者：
Dworkin, Lance D.
影响因子：
158.5
作者：
Ridker, PM;Cushman, M;Hennekens, CH
通讯作者：
Hennekens, CH