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LPS and palmitic acid Co-upregulate microglia activation and neuroinflammatory response

Growing evidence indicates that disturbances in the inflammatory response system can have deleterious effects on neuronal function and mental health. While the correlation between elevated peripheral inflammatory markers and psychiatric disorders are well documented, the exact molecular and neuronal...

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Autores principales: Lu, Zhongyang, Liu, Shufeng, Lopes-Virella, Maria F., Wang, Zhewu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9216426/
https://www.ncbi.nlm.nih.gov/pubmed/35757363
http://dx.doi.org/10.1016/j.cpnec.2021.100048
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author Lu, Zhongyang
Liu, Shufeng
Lopes-Virella, Maria F.
Wang, Zhewu
author_facet Lu, Zhongyang
Liu, Shufeng
Lopes-Virella, Maria F.
Wang, Zhewu
author_sort Lu, Zhongyang
collection PubMed
description Growing evidence indicates that disturbances in the inflammatory response system can have deleterious effects on neuronal function and mental health. While the correlation between elevated peripheral inflammatory markers and psychiatric disorders are well documented, the exact molecular and neuronal mechanism underlying the connection between activated inflammation and neuropsychiatric behaviour remain elusive. Microglia activation is the key interface between neuro-inflammation and manifestation of psychiatric symptoms. Microglia are immunocompetent cells in the central nervous system (CNS) which are primarily involved in the response to inflammatory stimulation and are widely used to study neuroinflammation and test anti-inflammatory chemicals. In the brain, activated microglia play very important roles during neuroinflammation and neurodegeneration. Both stress-related disorders such as Depression and PTSD, and medical conditions such as metabolic syndrome (Mets) and type 2 diabetes (TD2) are associated with increased levels of both saturated fatty acids (SFAs) and lipopolysaccharide (LPS) in circulation. This work was aimed at determining whether SFA interacts with LPS to activate microglia, thus up-regulating neuroinflammatory processes and, if so which pathways were involved in this process. Our results showed that low-dose LPS and palmitic acid (PA) robustly stimulated the expression of proinflammatory cytokines, and the combination of PA and LPS further upregulated proinflammatory cytokines through MAPK, NFκB and AP-1 signaling pathways in the HMC3-human microglial cell line. In addition, PA stimulated ceramide production via de novo synthesis and sphingomyelin hydrolysis, and the combination of LPS and PA further increased ceramide production. HMC3 co-cultured with macrophage and lymphocyte enhanced LPS and PA induced-inflammatory response more than that in HMC3 alone. These results indicate that LPS interacts with PA to activated microglia; induced neuroinflammatory responses, upregulate proinflammatory cytokine expression via MAPK, NFκB, and AP-1 signaling pathways, and induced sphingolipid metabolism in HMC3. These observations suggest that inhibiting microglia activation and reducing LPS and PA-induced inflammatory response may be useful in the treatment of neuronal inflammatory diseases.
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spelling pubmed-92164262022-06-24 LPS and palmitic acid Co-upregulate microglia activation and neuroinflammatory response Lu, Zhongyang Liu, Shufeng Lopes-Virella, Maria F. Wang, Zhewu Compr Psychoneuroendocrinol Clinical science Growing evidence indicates that disturbances in the inflammatory response system can have deleterious effects on neuronal function and mental health. While the correlation between elevated peripheral inflammatory markers and psychiatric disorders are well documented, the exact molecular and neuronal mechanism underlying the connection between activated inflammation and neuropsychiatric behaviour remain elusive. Microglia activation is the key interface between neuro-inflammation and manifestation of psychiatric symptoms. Microglia are immunocompetent cells in the central nervous system (CNS) which are primarily involved in the response to inflammatory stimulation and are widely used to study neuroinflammation and test anti-inflammatory chemicals. In the brain, activated microglia play very important roles during neuroinflammation and neurodegeneration. Both stress-related disorders such as Depression and PTSD, and medical conditions such as metabolic syndrome (Mets) and type 2 diabetes (TD2) are associated with increased levels of both saturated fatty acids (SFAs) and lipopolysaccharide (LPS) in circulation. This work was aimed at determining whether SFA interacts with LPS to activate microglia, thus up-regulating neuroinflammatory processes and, if so which pathways were involved in this process. Our results showed that low-dose LPS and palmitic acid (PA) robustly stimulated the expression of proinflammatory cytokines, and the combination of PA and LPS further upregulated proinflammatory cytokines through MAPK, NFκB and AP-1 signaling pathways in the HMC3-human microglial cell line. In addition, PA stimulated ceramide production via de novo synthesis and sphingomyelin hydrolysis, and the combination of LPS and PA further increased ceramide production. HMC3 co-cultured with macrophage and lymphocyte enhanced LPS and PA induced-inflammatory response more than that in HMC3 alone. These results indicate that LPS interacts with PA to activated microglia; induced neuroinflammatory responses, upregulate proinflammatory cytokine expression via MAPK, NFκB, and AP-1 signaling pathways, and induced sphingolipid metabolism in HMC3. These observations suggest that inhibiting microglia activation and reducing LPS and PA-induced inflammatory response may be useful in the treatment of neuronal inflammatory diseases. Elsevier 2021-03-17 /pmc/articles/PMC9216426/ /pubmed/35757363 http://dx.doi.org/10.1016/j.cpnec.2021.100048 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Clinical science
Lu, Zhongyang
Liu, Shufeng
Lopes-Virella, Maria F.
Wang, Zhewu
LPS and palmitic acid Co-upregulate microglia activation and neuroinflammatory response
title LPS and palmitic acid Co-upregulate microglia activation and neuroinflammatory response
title_full LPS and palmitic acid Co-upregulate microglia activation and neuroinflammatory response
title_fullStr LPS and palmitic acid Co-upregulate microglia activation and neuroinflammatory response
title_full_unstemmed LPS and palmitic acid Co-upregulate microglia activation and neuroinflammatory response
title_short LPS and palmitic acid Co-upregulate microglia activation and neuroinflammatory response
title_sort lps and palmitic acid co-upregulate microglia activation and neuroinflammatory response
topic Clinical science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9216426/
https://www.ncbi.nlm.nih.gov/pubmed/35757363
http://dx.doi.org/10.1016/j.cpnec.2021.100048
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