Cargando…

Decreased VEGFA alleviates the symptoms of LPS-induced sepsis in a mouse model by inhibiting glycolysis and thereby regulating the polarization of macrophages

The immune imbalance caused by excessive inflammatory reactions is the primary cause of sepsis. Macrophages with M1 and M2 polarization states are important immune cells that regulate the balance of the inflammatory response in sepsis. Encouraging the conversion of macrophages from the M1 to the M2...

Descripción completa

Detalles Bibliográficos
Autores principales: Lin, Jun, Jiang, Liping, Guo, Kun, Feng, Ning
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PAGEPress Publications, Pavia, Italy 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9827425/
https://www.ncbi.nlm.nih.gov/pubmed/36546420
http://dx.doi.org/10.4081/ejh.2023.3528
_version_ 1784867057260560384
author Lin, Jun
Jiang, Liping
Guo, Kun
Feng, Ning
author_facet Lin, Jun
Jiang, Liping
Guo, Kun
Feng, Ning
author_sort Lin, Jun
collection PubMed
description The immune imbalance caused by excessive inflammatory reactions is the primary cause of sepsis. Macrophages with M1 and M2 polarization states are important immune cells that regulate the balance of the inflammatory response in sepsis. Encouraging the conversion of macrophages from the M1 to the M2 type is an important strategy for relieving sepsis. Here, we demonstrated the upregulation of vascular endothelial growth factor A (VEGFA) in a mouse model of sepsis. Then, siRNA technology was applied to inhibit the expression of VEGFA in macrophages. Flow cytometry and RT‒qPCR results showed that low expression of VEGFA inhibited LPS-induced M1 polarization of macrophages. Decreased VEGFA was also proven to lower TNF-α, IL-1β, and IL-6 secretion by LPS-induced macrophages. In addition, the effects of knocking down VEGFA on the energy metabolism pattern of macrophages were investigated by glycolysis pressure tests and mitochondrial pressure tests, and VEGFA knockdown reversed the induction of glycolysis in macrophages by LPS. The mitochondrial content and ATP content results also confirmed this finding. After the tail vein of septic mice was injected with macrophages transfected with si-VEGFA, the liver and kidney damage and the pathological conditions of the lung were alleviated. The secretion of TNF-α and IL-6 was decreased, while IL-10 was increased in their serum. Immunohistochemical staining revealed decreased expression of CD86 and increased expression of CD206 in the si-VEGFA group. This study demonstrates that decreased VEGFA inhibits glycolysis and thus inhibits LPS-induced M1 polarization of macrophages, ultimately relieving sepsis.
format Online
Article
Text
id pubmed-9827425
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher PAGEPress Publications, Pavia, Italy
record_format MEDLINE/PubMed
spelling pubmed-98274252023-01-10 Decreased VEGFA alleviates the symptoms of LPS-induced sepsis in a mouse model by inhibiting glycolysis and thereby regulating the polarization of macrophages Lin, Jun Jiang, Liping Guo, Kun Feng, Ning Eur J Histochem Article The immune imbalance caused by excessive inflammatory reactions is the primary cause of sepsis. Macrophages with M1 and M2 polarization states are important immune cells that regulate the balance of the inflammatory response in sepsis. Encouraging the conversion of macrophages from the M1 to the M2 type is an important strategy for relieving sepsis. Here, we demonstrated the upregulation of vascular endothelial growth factor A (VEGFA) in a mouse model of sepsis. Then, siRNA technology was applied to inhibit the expression of VEGFA in macrophages. Flow cytometry and RT‒qPCR results showed that low expression of VEGFA inhibited LPS-induced M1 polarization of macrophages. Decreased VEGFA was also proven to lower TNF-α, IL-1β, and IL-6 secretion by LPS-induced macrophages. In addition, the effects of knocking down VEGFA on the energy metabolism pattern of macrophages were investigated by glycolysis pressure tests and mitochondrial pressure tests, and VEGFA knockdown reversed the induction of glycolysis in macrophages by LPS. The mitochondrial content and ATP content results also confirmed this finding. After the tail vein of septic mice was injected with macrophages transfected with si-VEGFA, the liver and kidney damage and the pathological conditions of the lung were alleviated. The secretion of TNF-α and IL-6 was decreased, while IL-10 was increased in their serum. Immunohistochemical staining revealed decreased expression of CD86 and increased expression of CD206 in the si-VEGFA group. This study demonstrates that decreased VEGFA inhibits glycolysis and thus inhibits LPS-induced M1 polarization of macrophages, ultimately relieving sepsis. PAGEPress Publications, Pavia, Italy 2022-12-22 /pmc/articles/PMC9827425/ /pubmed/36546420 http://dx.doi.org/10.4081/ejh.2023.3528 Text en ©Copyright: the Author(s) https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (by-nc 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Article
Lin, Jun
Jiang, Liping
Guo, Kun
Feng, Ning
Decreased VEGFA alleviates the symptoms of LPS-induced sepsis in a mouse model by inhibiting glycolysis and thereby regulating the polarization of macrophages
title Decreased VEGFA alleviates the symptoms of LPS-induced sepsis in a mouse model by inhibiting glycolysis and thereby regulating the polarization of macrophages
title_full Decreased VEGFA alleviates the symptoms of LPS-induced sepsis in a mouse model by inhibiting glycolysis and thereby regulating the polarization of macrophages
title_fullStr Decreased VEGFA alleviates the symptoms of LPS-induced sepsis in a mouse model by inhibiting glycolysis and thereby regulating the polarization of macrophages
title_full_unstemmed Decreased VEGFA alleviates the symptoms of LPS-induced sepsis in a mouse model by inhibiting glycolysis and thereby regulating the polarization of macrophages
title_short Decreased VEGFA alleviates the symptoms of LPS-induced sepsis in a mouse model by inhibiting glycolysis and thereby regulating the polarization of macrophages
title_sort decreased vegfa alleviates the symptoms of lps-induced sepsis in a mouse model by inhibiting glycolysis and thereby regulating the polarization of macrophages
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9827425/
https://www.ncbi.nlm.nih.gov/pubmed/36546420
http://dx.doi.org/10.4081/ejh.2023.3528
work_keys_str_mv AT linjun decreasedvegfaalleviatesthesymptomsoflpsinducedsepsisinamousemodelbyinhibitingglycolysisandtherebyregulatingthepolarizationofmacrophages
AT jiangliping decreasedvegfaalleviatesthesymptomsoflpsinducedsepsisinamousemodelbyinhibitingglycolysisandtherebyregulatingthepolarizationofmacrophages
AT guokun decreasedvegfaalleviatesthesymptomsoflpsinducedsepsisinamousemodelbyinhibitingglycolysisandtherebyregulatingthepolarizationofmacrophages
AT fengning decreasedvegfaalleviatesthesymptomsoflpsinducedsepsisinamousemodelbyinhibitingglycolysisandtherebyregulatingthepolarizationofmacrophages