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C-X-C Motif Chemokine 3 Promotes the Inflammatory Response of Microglia after Escherichia coli-Induced Meningitis
Meningitis is a major clinical manifestation of Escherichia coli (E. coli) infection characterized by inflammation of the meninges and subarachnoid space. Many chemokines are secreted during meningitic E. coli infection, of which C-X-C motif chemokine 3 (CXCL3) is the most highly expressed. However,...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10341832/ https://www.ncbi.nlm.nih.gov/pubmed/37445610 http://dx.doi.org/10.3390/ijms241310432 |
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author | Qu, Xinyi Dou, Beibei Yang, Ruicheng Tan, Chen Chen, Huanchun Wang, Xiangru |
author_facet | Qu, Xinyi Dou, Beibei Yang, Ruicheng Tan, Chen Chen, Huanchun Wang, Xiangru |
author_sort | Qu, Xinyi |
collection | PubMed |
description | Meningitis is a major clinical manifestation of Escherichia coli (E. coli) infection characterized by inflammation of the meninges and subarachnoid space. Many chemokines are secreted during meningitic E. coli infection, of which C-X-C motif chemokine 3 (CXCL3) is the most highly expressed. However, it is unclear how CXCL3 plays a role in meningitic E. coli infection. Therefore, this study used in vitro and in vivo assays to clarify these contributions and to identify novel therapeutic targets for central nervous system inflammation. We found a significantly upregulated expression of CXCL3 in human brain microvascular endothelial cells and U251 cells after meningitic E. coli infection, and the CXCL3 receptor, C-X-C motif chemokine receptor 2 (CXCR2), was expressed in microglia. Furthermore, CXCL3 induced M1 microglia by selectively activating mitogen-activated protein kinases signaling and significantly upregulating tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, nitric oxide synthase 2 (NOS2), and cluster of differentiation 86 (CD86) expression levels, promoting an inflammatory response. Our findings clarify the role of CXCL3 in meningitic E. coli-induced neuroinflammation and demonstrate that CXCL3 may be a potential therapeutic target for future investigation and prevention of E. coli-induced neuroinflammation. |
format | Online Article Text |
id | pubmed-10341832 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-103418322023-07-14 C-X-C Motif Chemokine 3 Promotes the Inflammatory Response of Microglia after Escherichia coli-Induced Meningitis Qu, Xinyi Dou, Beibei Yang, Ruicheng Tan, Chen Chen, Huanchun Wang, Xiangru Int J Mol Sci Article Meningitis is a major clinical manifestation of Escherichia coli (E. coli) infection characterized by inflammation of the meninges and subarachnoid space. Many chemokines are secreted during meningitic E. coli infection, of which C-X-C motif chemokine 3 (CXCL3) is the most highly expressed. However, it is unclear how CXCL3 plays a role in meningitic E. coli infection. Therefore, this study used in vitro and in vivo assays to clarify these contributions and to identify novel therapeutic targets for central nervous system inflammation. We found a significantly upregulated expression of CXCL3 in human brain microvascular endothelial cells and U251 cells after meningitic E. coli infection, and the CXCL3 receptor, C-X-C motif chemokine receptor 2 (CXCR2), was expressed in microglia. Furthermore, CXCL3 induced M1 microglia by selectively activating mitogen-activated protein kinases signaling and significantly upregulating tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, nitric oxide synthase 2 (NOS2), and cluster of differentiation 86 (CD86) expression levels, promoting an inflammatory response. Our findings clarify the role of CXCL3 in meningitic E. coli-induced neuroinflammation and demonstrate that CXCL3 may be a potential therapeutic target for future investigation and prevention of E. coli-induced neuroinflammation. MDPI 2023-06-21 /pmc/articles/PMC10341832/ /pubmed/37445610 http://dx.doi.org/10.3390/ijms241310432 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Qu, Xinyi Dou, Beibei Yang, Ruicheng Tan, Chen Chen, Huanchun Wang, Xiangru C-X-C Motif Chemokine 3 Promotes the Inflammatory Response of Microglia after Escherichia coli-Induced Meningitis |
title | C-X-C Motif Chemokine 3 Promotes the Inflammatory Response of Microglia after Escherichia coli-Induced Meningitis |
title_full | C-X-C Motif Chemokine 3 Promotes the Inflammatory Response of Microglia after Escherichia coli-Induced Meningitis |
title_fullStr | C-X-C Motif Chemokine 3 Promotes the Inflammatory Response of Microglia after Escherichia coli-Induced Meningitis |
title_full_unstemmed | C-X-C Motif Chemokine 3 Promotes the Inflammatory Response of Microglia after Escherichia coli-Induced Meningitis |
title_short | C-X-C Motif Chemokine 3 Promotes the Inflammatory Response of Microglia after Escherichia coli-Induced Meningitis |
title_sort | c-x-c motif chemokine 3 promotes the inflammatory response of microglia after escherichia coli-induced meningitis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10341832/ https://www.ncbi.nlm.nih.gov/pubmed/37445610 http://dx.doi.org/10.3390/ijms241310432 |
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