Targeting the phosphoinositide-3-kinase/protein kinase B pathway in airway innate immunity.
Targeting the phosphoinositide-3-kinase/protein kinase B pathway in airway innate immunity.
复制标题
靶向磷脂酰肌醇-3-激酶/蛋白激酶B通路在呼吸道天然免疫中的作用。
DOI：
10.4331/wjbc.v11.i2.30
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发表时间：
2020-09-27
期刊：
影响因子：
--
通讯作者：
Lee RJ
中科院分区：
文献类型：
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作者：
Gopallawa I;Lee RJ
呼吸道天然免疫系统是抵御呼吸道感染的第一道防线。呼吸道上皮和相关的免疫细胞保护呼吸系统免受外来生物的吸入。这些细胞通过激活Toll样受体和味觉家族2受体(T2Rs)等受体来感知病原体，并通过产生抗菌素、炎性细胞因子和趋化因子来做出反应。液体分泌和纤毛跳动的协调调节有助于通过粘液纤毛运输清除病原体。呼吸道细胞还分泌抗菌肽和自由基，直接杀死微生物和灭活病毒。肌醇磷脂-3-激酶/蛋白激酶B(Akt)通路调节多个细胞靶点，调节细胞的存活和增殖。AKT还调节与先天免疫途径有关的蛋白质。AKT可磷酸化呼吸道上皮细胞表达的内皮型一氧化氮合酶(ENOS)。ENOS的激活可以起到抗炎、抗菌和抗病毒的作用。此外，Akt还可以增加转录因子核因子红系2相关因子-2的活性，保护细胞免受氧化应激，并可能限制炎症。本文综述了Akt信号在呼吸道天然宿主防御机制中的非癌功能的最新研究结果，包括几个已知的Akt下游参与天然免疫的靶点。
The airway innate immune system maintains the first line of defense against respiratory infections. The airway epithelium and associated immune cells protect the respiratory system from inhaled foreign organisms. These cells sense pathogens via activation of receptors like toll-like receptors and taste family 2 receptors (T2Rs) and respond by producing antimicrobials, inflammatory cytokines, and chemokines. Coordinated regulation of fluid secretion and ciliary beating facilitates clearance of pathogens via mucociliary transport. Airway cells also secrete antimicrobial peptides and radicals to directly kill microorganisms and inactivate viruses. The phosphoinositide-3-kinase/protein kinase B (Akt) kinase pathway regulates multiple cellular targets that modulate cell survival and proliferation. Akt also regulates proteins involved in innate immune pathways. Akt phosphorylates endothelial nitric oxide synthase (eNOS) enzymes expressed in airway epithelial cells. Activation of eNOS can have anti-inflammatory, anti-bacterial, and anti-viral roles. Moreover, Akt can increase the activity of the transcription factor nuclear factor erythroid 2 related factor-2 that protects cells from oxidative stress and may limit inflammation. In this review, we summarize the recent findings of non-cancerous functions of Akt signaling in airway innate host defense mechanisms, including an overview of several known downstream targets of Akt involved in innate immunity.