PI3K-delta mediates double-stranded RNA-induced upregulation of B7-H1 in BEAS-2B airway epithelial cells
PI3K-delta mediates double-stranded RNA-induced upregulation of B7-H1 in BEAS-2B airway epithelial cells
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DOI：
10.1016/j.bbrc.2013.04.082
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发表时间：
2013-05-31
影响因子：
3.1
通讯作者：
Inoue, Hiromasa
中科院分区：
文献类型：
--
作者：
Kan-o, Keiko;Matsumoto, Koichiro;Inoue, Hiromasa
呼吸道病毒感染会影响健康相关的生活质量。B7-H1（也称为PD-L1）是一种共抑制分子，与病毒从粘膜免疫中逃逸相关，导致持续感染。大多数呼吸道病毒在复制过程中产生双链RNA。用类似病毒dsRNA的多肌苷-多胞苷酸（polyic）刺激培养的气道上皮细胞，通过激活核因子κ B（nf - κ B）上调B7-H1的表达。研究了与磷脂酰肌醇3-激酶（pi3k）相关的上调机制。在BEAS-2B细胞中，Poly - ic诱导的B7-H1上调被泛PI3K抑制剂深度抑制，部分被PI3K δ的抑制剂或小干扰RNA （si）抑制。在呼吸道合胞病毒感染的细胞中观察到类似的结果。Western blot检测p110 δ的表达，用PI3K δ siRNA预处理抑制p110 δ的表达。PI3K δ的活化通常是由氧化应激诱导的。聚IC增加了活性氧的产生。抗氧化剂n -乙酰- l-半胱氨酸或黄嘌呤氧化酶抑制剂氧嘌呤醇可以减弱聚IC诱导的B7-H1的上调。Poly - ic诱导的NF-kappa B的活化被pan-PI3K抑制剂抑制，而不被PI3K抑制剂抑制。这些结果表明，PI3K δ介导dsrna诱导的B7-H1的上调，而不影响NF-kappa b的激活(c) 2013 Elsevier Inc.。版权所有。
Airway viral infection disturbs the health-related quality of life. B7-H1 (also known as PD-L1) is a coinhibitory molecule associated with the escape of viruses from the mucosal immunity, leading to persistent infection. Most respiratory viruses generate double-stranded (ds) RNA during replication. The stimulation of cultured airway epithelial cells with an analog of viral dsRNA, polyinosinic-polycytidylic acid (poly IC) upregulates the expression of B7-H1 via activation of the nuclear factor kappa B(NF-kappa B). The mechanism of upregulation was investigated in association with phosphatidylinositol 3-kinases (PI3Ks). Poly IC-induced upregulation of B7-H1 was profoundly suppressed by a pan-PI3K inhibitor and partially by an inhibitor or a small interfering (si)RNA for PI3K delta in BEAS-2B cells. Similar results were observed in the respiratory syncytial virus-infected cells. The expression of p110 delta was detected by Western blot and suppressed by pretreatment with PI3K delta siRNA. The activation of PI3K delta is typically induced by oxidative stress. The generation of reactive oxygen species was increased by poly IC. Poly IC-induced upregulation of B7-H1 was attenuated by N-acetyl-L-cysteine, an antioxidant, or by oxypurinol, an inhibitor of xanthine oxidase. Poly IC-induced activation of NF-kappa B was suppressed by a pan-PI3K inhibitor but not by a PI3K delta inhibitor. These results suggest that PI3K delta mediates dsRNA-induced upregulation of B7-H1 without affecting the activation of NF-kappa B. (c) 2013 Elsevier Inc. All rights reserved.