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Epigallocatechin-3-gallate inhibits TLR4 signaling through the 67-kDa laminin receptor and effectively alleviates acute lung injury induced by H9N2 sw

tetano

Editor, Senior Moderator
nt Immunopharmacol. 2017 Aug 28;52:24-33. doi: 10.1016/j.intimp.2017.08.023. [Epub ahead of print] [h=1]Epigallocatechin-3-gallate inhibits TLR4 signaling through the 67-kDa laminin receptor and effectively alleviates acute lung injury induced by H9N2 swine influenza virus.[/h] Xu MJ[SUP]1[/SUP], Liu BJ[SUP]1[/SUP], Wang CL[SUP]1[/SUP], Wang GH[SUP]1[/SUP], Tian Y[SUP]1[/SUP], Wang SH[SUP]1[/SUP], Li J[SUP]1[/SUP], Li PY[SUP]1[/SUP], Zhang RH[SUP]1[/SUP], Wei D[SUP]1[/SUP], Tian SF[SUP]1[/SUP], Xu T[SUP]2[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] 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.
Copyright ? 2017 Elsevier B.V. All rights reserved.


[h=4]KEYWORDS:[/h] 67-kDa laminin receptor; Acute lung injury; Epigallocatechin-3-gallate; H9N2 swine influenza virus; Oxidative stress; Toll-like receptor 4

PMID: 28858723 DOI: 10.1016/j.intimp.2017.08.023
 
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