Protocatechuic acid and quercetin attenuate ETEC-caused IPEC-1 cell inflammation and injury associated with inhibition of necroptosis and pyroptosis signaling pathways  

作　　者：Kan Xiao Mohan Zhou Qingqing Lv Pengwei He Xu Qin Dan Wang Jiangchao Zhao Yulan Liu 

机构地区：[1]Hubei Key Laboratory of Animal Nutrition and Feed Science,Wuhan Polytechnic University,Wuhan 430023,People’s Republic of China [2]Department of Animal Science,Division of Agriculture,University of Arkansas,Fayetteville,AR 72701,USA

出　　处：《Journal of Animal Science and Biotechnology》2023年第4期1551-1568,共18页畜牧与生物技术杂志（英文版）

基　　金：provided by National Key R&D Program of China(2022YFD1300403);National Natural Science Foundation of China(No.U22A20517,32272906,and 31802070);Wuhan Science and Technology Bureau(No.2022020801010391)。

摘　　要：Background:Necroptosis and pyroptosis are newly identified forms of programmed cell death,which play a vital role in development of many gastrointestinal disorders.Although plant polyphenols have been reported to protect intestinal health,it is still unclear whether there is a beneficial role of plant polyphenols in modulating necroptosis and pyroptosis in intestinal porcine epithelial cell line(IPEC-1)infected with enterotoxigenic Escherichia coli(ETEC)K88.This research was conducted to explore whether plant polyphenols including protocatechuic acid(PCA)and quercetin(Que),attenuated inflammation and injury of IPEC-1 caused by ETEC K88 through regulating necroptosis and pyroptosis signaling pathways.Methods:IPEC-1 cells were treated with PCA(40μmol/L)or Que(10μmol/L)in the presence or absence of ETEC K88.Results:PCA and Que decreased ETEC K88 adhesion and endotoxin level(P<0.05)in cell supernatant.PCA and Que increased cell number(P<0.001)and decreased lactate dehydrogenases(LDH)activity(P<0.05)in cell supernatant after ETEC infection.PCA and Que improved transepithelial electrical resistance(TEER)(P<0.001)and reduced fluorescein isothiocyanate-labeled dextran(FD4)flux(P<0.001),and enhanced membrane protein abundance of occludin,claudin-1 and ZO-1(P<0.05),and rescued distribution of these tight junction proteins(P<0.05)after ETEC infection.PCA and Que also declined cell necrosis ratio(P<0.05).PCA and Que reduced mRNA abundance and concentration of tumor necrosis factor-α(TNF-α),interleukin(IL)-6 and IL-8(P<0.001),and down-regulated gene expression of toll-like receptors 4(TLR4)and its downstream signals(P<0.001)after ETEC infection.PCA and Que down-regulated protein abundance of total receptor interacting protein kinase 1(t-RIP1),phosphorylated-RIP1(p-RIP1),p-RIP1/t-RIP1,t-RIP3,p-RIP3,mixed lineage kinase domain-like protein(MLKL),p-MLKL,dynamin-related protein 1(DRP1),phosphoglycerate mutase 5(PGAM5)and high mobility group box 1(HMGB1)(P<0.05)after ETEC infection.Moreover,PCA and Que reduced protein abundanc

关 键 词：Cell damage ETEC K88 Intestinal inflammation NECROPTOSIS Protocatechuic acid PYROPTOSIS QUERCETIN 

分 类 号：S816.7[农业科学—饲料科学]