Defects in actin dynamics lead to an autoinflammatory condition through the upregulation of CXCL5.
Defects in actin dynamics lead to an autoinflammatory condition through the upregulation of CXCL5.
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DOI：
10.1371/journal.pone.0002701
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发表时间：
2008-07-16
期刊：
影响因子：
3.7
通讯作者：
Ikeda, Sakae
中科院分区：
文献类型：
--
作者：
Verdoni, Angela M.;Smith, Richard S.;Ikeda, Akihiro;Ikeda, Sakae
Destrin（Destrin）是ADF/cofilin蛋白家族的成员，并且是肌动蛋白动力学的重要调节剂。destrin的主要功能是将丝状肌动蛋白降解成单体形式并促进丝状肌动蛋白的切断。虽然在理解ADF/cofilin蛋白的生物化学功能方面取得了进展，但对DAF缺陷细胞的动物模型的研究提供了一个机会来研究体内由适当的肌动蛋白动力学调节的生理过程。一种自发的小鼠突变体，角膜疾病1（corn 1），是缺乏Dopamine，这会导致上皮细胞过度增殖和角膜新生血管形成。Dstncorn 1小鼠表现出肌动蛋白动力学缺陷，在角膜的上皮细胞中的肌动蛋白应力纤维的形成证明。以前，我们观察到白细胞显著浸润到Dstncorn 1小鼠的角膜中，以及促炎分子的上调。在这项研究中，我们试图描述这种炎症状况，并探索Doppler功能丧失导致炎症的生理机制。通过免疫荧光分析，我们观察到一个显着的招聘中性粒细胞和巨噬细胞的Dstncorn 1角膜，表明先天免疫系统是自发激活的突变体。炎性趋化因子CXCL 5在Dstncorn 1小鼠的角膜上皮细胞中异位表达，靶向该趋化因子的受体抑制了中性粒细胞的募集。在等位基因突变株Dstncorn 1 - 2 J的角膜中未观察到炎症反应，Dstncorn 1 - 2 J在角膜上皮细胞中的肌动蛋白动力学中具有较轻的缺陷。这项研究表明，肌动蛋白动力学的严重缺陷导致CXC趋化因子表达介导的自身炎症状态。
Destrin (DSTN) is a member of the ADF/cofilin family of proteins and is an important regulator of actin dynamics. The primary function of destrin is to depolymerize filamentous actin into its monomeric form and promote filament severing. While progress has been made in understanding the biochemical functions of the ADF/cofilin proteins, the study of an animal model for cells deficient for DSTN provides an opportunity to investigate the physiological processes regulated by proper actin dynamics in vivo. A spontaneous mouse mutant, corneal disease 1(corn1), is deficient for DSTN, which causes epithelial hyperproliferation and neovascularization in the cornea. Dstncorn1 mice exhibit an actin dynamics defect in the cornea as evidenced by the formation of actin stress fibers in the epithelial cells. Previously, we observed a significant infiltration of leukocytes into the cornea of Dstncorn1 mice as well as the upregulation of proinflammatory molecules. In this study, we sought to characterize this inflammatory condition and explore the physiological mechanism through which a loss of Dstn function leads to inflammation. Through immunofluorescent analyses, we observed a significant recruitment of neutrophils and macrophages to the Dstncorn1 cornea, demonstrating that the innate immune system is spontaneously activated in this mutant. The inflammatory chemokine, CXCL5, was ectopically expressed in the corneal epithelial cells of Dstncorn1 mice, and targeting of the receptor for this chemokine inhibited neutrophil recruitment. An inflammatory reaction was not observed in the cornea of allelic mutant strain, Dstncorn1-2J, which has a milder defect in actin dynamics in the corneal epithelial cells. This study shows that severe defects in actin dynamics lead to an autoinflammatory condition that is mediated by the expression of CXC chemokines.
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影响因子：
4.4
作者：
Hall, LR;Diaconu, E;Pearlman, E
通讯作者：
Pearlman, E
肌动蛋白去聚合因子（ADF/Cofilin）提高了细丝流动率：基于肌动蛋白的运动的影响。
DOI：
10.1083/jcb.136.6.1307
发表时间：
1997-03-24
期刊：
The Journal of cell biology
影响因子：
--
作者：
Carlier MF;Laurent V;Santolini J;Melki R;Didry D;Xia GX;Hong Y;Chua NH;Pantaloni D
通讯作者：
Pantaloni D
影响因子：
3.7
作者：
Gonçalves, AS;Appelberg, R
通讯作者：
Appelberg, R
影响因子：
3.8
作者：
Feniger-Barish, R;Ran, M;Ben-Baruch, A
通讯作者：
Ben-Baruch, A
DOI：
10.1083/jcb.131.5.1243
发表时间：
1995-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gunsalus KC;Bonaccorsi S;Williams E;Verni F;Gatti M;Goldberg ML
通讯作者：
Goldberg ML