Propionic Acid Targets the TLR4/NF-κB Signaling Pathway and Inhibits LPS-Induced Intestinal Barrier Dysfunction: In Vitro and In Vivo Studies

Intestinal barrier dysfunction contributes to the development of intestinal diseases. Propionic acid (PA), a metabolite generated by anaerobic fermentation of dietary fiber in the intestinal cavity, has been proved to exert anti-inflammatory effects in a variety of diseases. However, the exact role...

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Main Authors: Randong Yang, Xiaoxiao Hu, Xianzheng Xie, Haiqiong Chen, Huangyi Fang, Libing Zhu, Zhongrong Li
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-09-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fphar.2020.573475/full
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author Randong Yang
Xiaoxiao Hu
Xianzheng Xie
Haiqiong Chen
Huangyi Fang
Libing Zhu
Zhongrong Li
author_facet Randong Yang
Xiaoxiao Hu
Xianzheng Xie
Haiqiong Chen
Huangyi Fang
Libing Zhu
Zhongrong Li
author_sort Randong Yang
collection DOAJ
description Intestinal barrier dysfunction contributes to the development of intestinal diseases. Propionic acid (PA), a metabolite generated by anaerobic fermentation of dietary fiber in the intestinal cavity, has been proved to exert anti-inflammatory effects in a variety of diseases. However, the exact role of PA in LPS-induced intestinal barrier dysfunction is still unclear. Accordingly, we examined the latent mechanism of PA and its protective role in LPS-induced intestinal barrier dysfunction by both in vitro and in vivo experiments. In vitro, we identified that PA treatment could strongly promote cell migration, inhibit activation of NLRP3 inflammasome and maintain intestinal barrier function in LPS-induced IEC-6 cells, indicating the protective effect on the intestinal barrier function of PA. Further investigation of the mechanism involved revealed that PA could suppress the activation of TLR4/NF-κB pathway. In vivo, in a LPS-induced rat model, PA-induced protective effects in intestinal barrier dysfunction could be detected. In summary, our findings clarify the role of PA in intestinal barrier dysfunction and suggest that it is promising for the treatment of LPS-related intestinal diseases.
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spelling doaj.art-b386464db0c84cd29925663de54de45a2022-12-22T00:07:01ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-09-011110.3389/fphar.2020.573475573475Propionic Acid Targets the TLR4/NF-κB Signaling Pathway and Inhibits LPS-Induced Intestinal Barrier Dysfunction: In Vitro and In Vivo StudiesRandong Yang0Xiaoxiao Hu1Xianzheng Xie2Haiqiong Chen3Huangyi Fang4Libing Zhu5Zhongrong Li6Department of Pediatric Surgery, The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Pediatric Surgery, The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Pediatric Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Pediatric Surgery, The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Pediatric Surgery, The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Pediatric Surgery, The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Pediatric Surgery, The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaIntestinal barrier dysfunction contributes to the development of intestinal diseases. Propionic acid (PA), a metabolite generated by anaerobic fermentation of dietary fiber in the intestinal cavity, has been proved to exert anti-inflammatory effects in a variety of diseases. However, the exact role of PA in LPS-induced intestinal barrier dysfunction is still unclear. Accordingly, we examined the latent mechanism of PA and its protective role in LPS-induced intestinal barrier dysfunction by both in vitro and in vivo experiments. In vitro, we identified that PA treatment could strongly promote cell migration, inhibit activation of NLRP3 inflammasome and maintain intestinal barrier function in LPS-induced IEC-6 cells, indicating the protective effect on the intestinal barrier function of PA. Further investigation of the mechanism involved revealed that PA could suppress the activation of TLR4/NF-κB pathway. In vivo, in a LPS-induced rat model, PA-induced protective effects in intestinal barrier dysfunction could be detected. In summary, our findings clarify the role of PA in intestinal barrier dysfunction and suggest that it is promising for the treatment of LPS-related intestinal diseases.https://www.frontiersin.org/article/10.3389/fphar.2020.573475/fullpropionic acidlipopolysaccharideintestinal barriercell migrationNLRP3 inflammasome
spellingShingle Randong Yang
Xiaoxiao Hu
Xianzheng Xie
Haiqiong Chen
Huangyi Fang
Libing Zhu
Zhongrong Li
Propionic Acid Targets the TLR4/NF-κB Signaling Pathway and Inhibits LPS-Induced Intestinal Barrier Dysfunction: In Vitro and In Vivo Studies
Frontiers in Pharmacology
propionic acid
lipopolysaccharide
intestinal barrier
cell migration
NLRP3 inflammasome
title Propionic Acid Targets the TLR4/NF-κB Signaling Pathway and Inhibits LPS-Induced Intestinal Barrier Dysfunction: In Vitro and In Vivo Studies
title_full Propionic Acid Targets the TLR4/NF-κB Signaling Pathway and Inhibits LPS-Induced Intestinal Barrier Dysfunction: In Vitro and In Vivo Studies
title_fullStr Propionic Acid Targets the TLR4/NF-κB Signaling Pathway and Inhibits LPS-Induced Intestinal Barrier Dysfunction: In Vitro and In Vivo Studies
title_full_unstemmed Propionic Acid Targets the TLR4/NF-κB Signaling Pathway and Inhibits LPS-Induced Intestinal Barrier Dysfunction: In Vitro and In Vivo Studies
title_short Propionic Acid Targets the TLR4/NF-κB Signaling Pathway and Inhibits LPS-Induced Intestinal Barrier Dysfunction: In Vitro and In Vivo Studies
title_sort propionic acid targets the tlr4 nf κb signaling pathway and inhibits lps induced intestinal barrier dysfunction in vitro and in vivo studies
topic propionic acid
lipopolysaccharide
intestinal barrier
cell migration
NLRP3 inflammasome
url https://www.frontiersin.org/article/10.3389/fphar.2020.573475/full
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