Animal Science College, Hebei North University, Zhangjiakou 075131, PR China.
Animal Science College, Hebei North University, Zhangjiakou 075131, PR China.
Int Immunopharmacol. 2017 Nov;52:24-33. doi: 10.1016/j.intimp.2017.08.023. Epub 2017 Aug 31.
Epigallocatechin-3-gallate (EGCG) was found to inhibit the Toll-like receptor 4 (TLR4) pathway involved in influenza virus pathogenesis. Here, the effect of EGCG on TLR4 in an H9N2 virus-induced acute lung injury mouse model was investigated. BALB/c mice were inoculated intranasally with A/Swine/Hebei/108/2002 (H9N2) virus or noninfectious allantoic fluid, and treated with EGCG and E5564 or normal saline orally for 5 consecutive days. PMVECs were treated with EGCG or anti-67kDa laminin receptor (LR). Lung physiopathology, inflammation, oxidative stress, viral replication, and TLR4/NF-κB/Toll-interacting protein (Tollip) pathway in lung tissue and/or PMVECs were investigated. EGCG attenuated lung histological lesions, decreased lung W/D ratio, cytokines levels, and inhibited MPO activity and prolonged mouse survival. EGCG treatment also markedly downregulated TLR4 and NF-κB protein levels but Tollip expression was upregulated compared with that in untreated H9N2-infected mice (P<0.05). In PMVECs, anti-67LR antibody treatment significantly downregulated Tollip levels; however, the TLR4 and NF-κB protein levels dramatically increased compared with that in the EGCG-treated group (P<0.05). EGCG remarkably downregulated TLR4 protein levels through 67LR/Tollip, decreased MPO activity and inflammatory cytokine levels, supporting EGCG as a potential therapeutic agent for managing acute lung injury induced by H9N2 SIV.
没食子儿茶素-3-没食子酸酯（EGCG）被发现可抑制流感病毒发病机制中涉及的 Toll 样受体 4（TLR4）途径。在这里，研究了 EGCG 在 H9N2 病毒诱导的急性肺损伤小鼠模型中对 TLR4 的影响。BALB/c 小鼠经鼻腔接种 A/Swine/Hebei/108/2002（H9N2）病毒或无感染性鸡胚尿囊液，并连续 5 天口服 EGCG 和 E5564 或生理盐水进行治疗。用 EGCG 或抗 67kDa 层粘连蛋白受体（LR）处理 PMVECs。研究了 EGCG 或抗 67kDa 层粘连蛋白受体（LR）处理 PMVECs 对肺组织和/或 PMVECs 中肺生理病理学、炎症、氧化应激、病毒复制以及 TLR4/NF-κB/Toll 相互作用蛋白（Tollip）途径的影响。EGCG 减轻了肺组织学损伤，降低了肺湿/干重比，降低了细胞因子水平，并抑制了 MPO 活性，延长了小鼠的存活时间。与未处理的 H9N2 感染小鼠相比，EGCG 治疗还显著下调了 TLR4 和 NF-κB 蛋白水平，但 Tollip 表达上调（P<0.05）。在 PMVECs 中，抗 67LR 抗体处理显著下调了 Tollip 水平；然而，与 EGCG 处理组相比，TLR4 和 NF-κB 蛋白水平显著增加（P<0.05）。EGCG 通过 67LR/Tollip 显著下调 TLR4 蛋白水平，降低 MPO 活性和炎症细胞因子水平，表明 EGCG 可能是治疗 H9N2 SIV 诱导的急性肺损伤的潜在治疗剂。
