The critical role of lipopolysaccharide in the upregulation of aquaporin 4 in glial cells treated with Shiga toxin.
The critical role of lipopolysaccharide in the upregulation of aquaporin 4 in glial cells treated with Shiga toxin.
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DOI：
10.1186/s12929-015-0184-5
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发表时间：
2015-09-18
影响因子：
11
通讯作者：
Yachie A
中科院分区：
文献类型：
--
作者：
Sugimoto N;Leu H;Inoue N;Shimizu M;Toma T;Kuroda M;Saito T;Wada T;Yachie A
2011年，日本爆发了产志贺毒素大肠杆菌（STEC）感染。大约62%的溶血性尿毒症综合征患者还表现出脑病症状。为了确定产志在大肠杆菌感染期间脑病发病的机制，我们对神经胶质细胞系和原代神经胶质细胞进行了体外研究。志贺毒素2 （Stx-2）与脂多糖（LPS）联合或单独激活胶质细胞中的核因子-κB （NF-κB）信号。同样，Stx-2与LPS联合或单独使用LPS均可增加胶质细胞中水通道蛋白4 （AQP4）的表达水平。这可能是由于AQP4的过表达导致渗透水通过质膜迅速增加流入细胞，从而诱导细胞肿胀和脑水肿。我们最近发现Stx-2和LPS联合使用可诱导神经胶质细胞凋亡。神经胶质细胞是维持大脑稳态所不可缺少的细胞；因此，它们的功能障碍和死亡损害了大脑的内稳态并导致脑病。我们假设STEC感染的脑病发生在Stx-2攻击血脑屏障的血管内皮细胞并诱导其死亡时。然后Stx-2和LPS攻击不再与内皮细胞接触的暴露的神经胶质细胞。AQP4在神经胶质细胞中过度表达，导致其肿胀并对大脑稳态产生不利影响。一旦大脑稳态以这种方式受到影响，产志贺毒素大肠杆菌患者可能会出现脑病。本文的在线版本（doi:10.1186/s12929-015- 0185 -5）包含补充材料，可供授权用户使用。
In 2011, there was an outbreak of Shiga toxin-producing Escherichia coli (STEC) infections in Japan. Approximately 62 % of patients with hemolytic-uremic syndrome also showed symptoms of encephalopathy. To determine the mechanisms of onset for encephalopathy during STEC infections, we conducted an in vitro study with glial cell lines and primary glial cells. Shiga toxin 2 (Stx-2) in combination with lipopolysaccharide (LPS), or LPS alone activates nuclear factor-κB (NF-κB) signaling in glial cells. Similarly, Stx-2 in combination with LPS, or LPS alone increases expression levels of aquaporin 4 (AQP4) in glial cells. It is possible that overexpression of AQP4 results in a rapid and increased influx of osmotic water across the plasma membrane into cells, thereby inducing cell swelling and cerebral edema. We have showed that a combination of Stx-2 and LPS induced apoptosis of glial cells recently. Glial cells are indispensable for cerebral homeostasis; therefore, their dysfunction and death impairs cerebral homeostasis and results in encephalopathy. We postulate that the onset of encephalopathy in STEC infections occurs when Stx-2 attacks vascular endothelial cells of the blood–brain barrier, inducing their death. Stx-2 and LPS then attack the exposed glial cells that are no longer in contact with the endothelial cells. AQP4 is overexpressed in glial cells, resulting in their swelling and adversely affecting cerebral homeostasis. Once cerebral homeostasis is affected in such a way, encephalopathy is the likely result in STEC patients. The online version of this article (doi:10.1186/s12929-015-0184-5) contains supplementary material, which is available to authorized users.