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首页> 外文期刊>Open Journal of Pathology >Gα12 Regulates Interleukin-8 Expression after Epithelial Cell Injury
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Gα12 Regulates Interleukin-8 Expression after Epithelial Cell Injury

机译：Gα12调节上皮细胞损伤后白细胞介素8表达

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Acute kidney injury (AKI) is common in hospitalized patients and is strongly correlated with increased morbidity, mortality, and prolonged hospitalization. However, signals that determine whether injured tissues following AKI will repair or fibrose and lead to chronic kidney disease (CKD) are not well defined. Numerous cytokines are activated at various times after injury and recruit inflammatory cells. Interleukin-8 (IL-8) is upregulated following activation of Gα12 by H2O2, a reactive oxygen species (ROS). Herein, we study this occurrence in vitro and in vivo. IL-8 was measured by ELISA in Gα12-silenced (si-Gα12) and inducible QLα12 (constitutively active Gα12) Madin-Darby Canine Kidney (QLα12-MDCK) cell lines after H2O2/catalase cell injury. QLα12- and si-Gα12 MDCK cells showed time-, agonist- and Gα12-dependent increases in IL-8 mRNA and protein. Gα12-silenced MDCK cells demonstrated lower IL-8 expression and blunted IL-8 increases. In transgenic mice (QLα12γGTCre+, proximal tubule Qα12 expression) ischemia reperfusion injury led to significant upregulation of CXCL-1 (IL-8 homologue) at 48 hours that was not observed in Gα12 knockout mice. Macrophages in renal cells from these mice were imaged by immunofluorescent microscopy and QLα12γGTCre+ showed increased macrophage infiltration. We demonstrate that IL-8 is a critical link between H2O2 stimulated Gα12 and renal injury. Gα12 activation led to increased IL-8 expression, a potent mediator of inflammation after injury. Future studies targeting Gα12 for inhibition after injury may blunt the IL-8 response and allow for organ recovery.
机译：急性肾损伤（AKI）在住院患者中很常见，并且与发病率，死亡率增加和住院时间延长密切相关。但是，不能确定确定AKI后受损组织是否会修复或纤维化并导致慢性肾脏疾病（CKD）的信号。在损伤后的不同时间激活许多细胞因子并募集炎性细胞。 H2O2（一种活性氧（ROS））激活Gα12后，白细胞介素8（IL-8）上调。在本文中，我们在体外和体内研究这种情况。通过H2O2 /过氧化氢酶细胞损伤后的Gα12沉默（si-Gα12）和可诱导的QLα12（组成型活性Gα12）Madin-Darby犬肾（QLα12-MDCK）细胞系通过ELISA测量IL-8。 QLα12和si-Gα12MDCK细胞在IL-8 mRNA和蛋白质中显示出时间依赖性，激动剂依赖性和Gα12依赖性增加。 Gα12沉默的MDCK细胞表现出较低的IL-8表达，而钝化的IL-8增加。在转基因小鼠（QLα12γGTCre+，近端小管Qα12表达）中，缺血再灌注损伤导致48小时时CXCL-1（IL-8同源物）显着上调，而在Gα12基因敲除小鼠中未观察到。通过免疫荧光显微镜对这些小鼠肾细胞中的巨噬细胞进行成像，QLα12γGTCre+显示巨噬细胞浸润增加。我们证明，IL-8是H2O2刺激的Gα12与肾损伤之间的关键环节。 Gα12激活导致IL-8表达增加，IL-8表达是受伤后炎症的有效介体。今后针对Gα12进行损伤后抑制的研究可能会减弱IL-8反应并允许器官恢复。

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