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Kynurenic acid inhibits macrophage pyroptosis by suppressing ROS production via activation of the NRF2 pathway

Macrophage pyroptosis and related inflammatory responses play an important role in periodontitis. Kynurenic acid (KA) is hypothesized to have anti-inflammatory potential, but whether KA can inhibit macrophage pyroptosis and the underlying mechanisms remain unclear. Lipopolysaccharide (LPS) was used...

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Autores principales: Gao, Yuwei, Guo, Xiaohui, Zhou, Yunpeng, Du, Jie, Lu, Chengbo, Zhang, Lei, Sun, Siyuan, Wang, Shengfang, Li, Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10552067/
https://www.ncbi.nlm.nih.gov/pubmed/37772394
http://dx.doi.org/10.3892/mmr.2023.13098
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author Gao, Yuwei
Guo, Xiaohui
Zhou, Yunpeng
Du, Jie
Lu, Chengbo
Zhang, Lei
Sun, Siyuan
Wang, Shengfang
Li, Yang
author_facet Gao, Yuwei
Guo, Xiaohui
Zhou, Yunpeng
Du, Jie
Lu, Chengbo
Zhang, Lei
Sun, Siyuan
Wang, Shengfang
Li, Yang
author_sort Gao, Yuwei
collection PubMed
description Macrophage pyroptosis and related inflammatory responses play an important role in periodontitis. Kynurenic acid (KA) is hypothesized to have anti-inflammatory potential, but whether KA can inhibit macrophage pyroptosis and the underlying mechanisms remain unclear. Lipopolysaccharide (LPS) was used to induce pyroptosis in THP-1-derived macrophages. KA or ML385 was used to pretreat macrophages, after which, cell viability, NOD-like receptor protein 3 (NLRP3) inflammasome-related protein expression, oxidative stress levels and nuclear factor erythroid 2-related factor 2 (NRF2) expression were measured. The results showed that KA improved the LPS-induced decrease in macrophage viability and lactate dehydrogenase release. KA prevented THP-1 macrophage pyroptosis induced by LPS by reducing the expression of NLRP3, Gasdermin-D, and Caspase1, and decreased the expression of inflammatory factors. KA suppressed NLRP3 inflammasome activation by inhibiting ROS overproduction and increasing Heme Oxygenase 1 and glutathione levels. Moreover, KA promoted NRF2 translocation from the cytoplasm to the nucleus. In addition, the anti-pyroptotic and antioxidant effects of KA were reversed by ML385 inhibition of NRF2. In the present study, it was found that KA significantly suppressed macrophage pyroptosis induced by LPS. It was further demonstrated that the anti-pyroptotic effects of KA were mediated by activation of the NRF2 pathway.
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spelling pubmed-105520672023-10-06 Kynurenic acid inhibits macrophage pyroptosis by suppressing ROS production via activation of the NRF2 pathway Gao, Yuwei Guo, Xiaohui Zhou, Yunpeng Du, Jie Lu, Chengbo Zhang, Lei Sun, Siyuan Wang, Shengfang Li, Yang Mol Med Rep Articles Macrophage pyroptosis and related inflammatory responses play an important role in periodontitis. Kynurenic acid (KA) is hypothesized to have anti-inflammatory potential, but whether KA can inhibit macrophage pyroptosis and the underlying mechanisms remain unclear. Lipopolysaccharide (LPS) was used to induce pyroptosis in THP-1-derived macrophages. KA or ML385 was used to pretreat macrophages, after which, cell viability, NOD-like receptor protein 3 (NLRP3) inflammasome-related protein expression, oxidative stress levels and nuclear factor erythroid 2-related factor 2 (NRF2) expression were measured. The results showed that KA improved the LPS-induced decrease in macrophage viability and lactate dehydrogenase release. KA prevented THP-1 macrophage pyroptosis induced by LPS by reducing the expression of NLRP3, Gasdermin-D, and Caspase1, and decreased the expression of inflammatory factors. KA suppressed NLRP3 inflammasome activation by inhibiting ROS overproduction and increasing Heme Oxygenase 1 and glutathione levels. Moreover, KA promoted NRF2 translocation from the cytoplasm to the nucleus. In addition, the anti-pyroptotic and antioxidant effects of KA were reversed by ML385 inhibition of NRF2. In the present study, it was found that KA significantly suppressed macrophage pyroptosis induced by LPS. It was further demonstrated that the anti-pyroptotic effects of KA were mediated by activation of the NRF2 pathway. D.A. Spandidos 2023-09-22 /pmc/articles/PMC10552067/ /pubmed/37772394 http://dx.doi.org/10.3892/mmr.2023.13098 Text en Copyright: © Gao et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Gao, Yuwei
Guo, Xiaohui
Zhou, Yunpeng
Du, Jie
Lu, Chengbo
Zhang, Lei
Sun, Siyuan
Wang, Shengfang
Li, Yang
Kynurenic acid inhibits macrophage pyroptosis by suppressing ROS production via activation of the NRF2 pathway
title Kynurenic acid inhibits macrophage pyroptosis by suppressing ROS production via activation of the NRF2 pathway
title_full Kynurenic acid inhibits macrophage pyroptosis by suppressing ROS production via activation of the NRF2 pathway
title_fullStr Kynurenic acid inhibits macrophage pyroptosis by suppressing ROS production via activation of the NRF2 pathway
title_full_unstemmed Kynurenic acid inhibits macrophage pyroptosis by suppressing ROS production via activation of the NRF2 pathway
title_short Kynurenic acid inhibits macrophage pyroptosis by suppressing ROS production via activation of the NRF2 pathway
title_sort kynurenic acid inhibits macrophage pyroptosis by suppressing ros production via activation of the nrf2 pathway
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10552067/
https://www.ncbi.nlm.nih.gov/pubmed/37772394
http://dx.doi.org/10.3892/mmr.2023.13098
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