ResolvinD1 Protects the Airway Barrier Against Injury Induced by Influenza A Virus Through the Nrf2 Pathway.
ResolvinD1 Protects the Airway Barrier Against Injury Induced by Influenza A Virus Through the Nrf2 Pathway.
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ResolvinD1 通过 Nrf2 途径保护气道屏障免受甲型流感病毒引起的损伤。
DOI：
10.3389/fcimb.2020.616475
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发表时间：
2020
影响因子：
5.7
通讯作者：
Fei GH
中科院分区：
文献类型：
--
作者：
Guo Y;Tu YH;Wu X;Ji S;Shen JL;Wu HM;Fei GH
甲型流感病毒（IAV）引起的气道屏障损伤和过度炎症与疾病进展和预后相关。ResolvinD 1（RvD 1）是一种有前途的脂质介质，对肺部感染具有重要的保护作用。然而，RvD 1是否保护免受IAV诱导的损伤及其潜在机制仍然难以捉摸。在这项研究中，原代正常人支气管上皮细胞（pNHBE）分离和共培养IAV和/或RvD 1。检测E-cadherin、Zonula occludins-1、炎症介质及Nrf 2依赖性通路蛋白的表达。为了进一步探讨其作用机制，将Nrf 2短发夹RNA（Nrf 2 shRNA）应用于pNHBE细胞。此外，小鼠感染IAV，随后用RvD 1治疗。结果表明，IAV可下调E-cadherin、Zonula occludins-1、Nrf 2和HO-1的表达，上调NF κ B B p65和IKB B α的磷酸化，上调IL-8和TNF-α的水平，并上调ROS的产生。RvD 1逆转了IAV诱导的这些损伤作用。然而，当在pNHBE细胞中用shRNA抑制Nrf 2表达时，RvD 1对IAV诱导的损伤的保护作用被抑制。体内研究进一步证明RvD 1可以减轻屏障蛋白的破坏，减少气道炎症反应。总的来说，该研究表明，RvD 1可以通过Nrf 2途径在保护气道上皮屏障功能和减少炎症方面发挥双重有益作用，这可能为甲型流感病毒感染提供更好的治疗选择。
Airway barrier damage and excessive inflammation induced by influenza A virus (IAV) are associated with disease progression and prognosis. ResolvinD1 (RvD1) is a promising lipid mediator with critical protection against infection in the lung. However, whether RvD1 protects against IAV-induced injury and the underlying mechanisms remain elusive. In this study, primary normal human bronchial epithelial (pNHBE) cells were isolated and co-cultured with IAV and/or RvD1. Then, the expressions of E-cadherin, Zonula occludins-1, inflammatory mediators and proteins in Nrf2-dependent pathway were detected. To further explore the mechanisms, Nrf2 short hairpin RNA (Nrf2 shRNA) was applied in pNHBE cells. Furthermore, mice were infected with IAV, and were subsequently treated with RvD1. We found that IAV downregulated expressions of E-cadherin, Zonula occludins-1, Nrf2 and HO-1, upregulated the phosphorylation of NF κ B p65 and IKBα, levels of IL-8 and TNF-α, as well as ROS production. RvD1 reversed these damaging effects induced by IAV. However, when Nrf2 expression was suppressed with shRNA in pNHBE cells, the protective effects of RvD1 on IAV-induced injury were inhibited. In vivo studies further demonstrated that RvD1 could alleviate barrier protein breakdown and reduce airway inflammatory reactions. Collectively, the study demonstrated that RvD1 could play dual beneficial roles in protecting airway epithelium barrier function and reducing inflammation via the Nrf2 pathway, which may provide a better treatment option for influenza A virus infection.