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Dexamethasone inhibits IL-8 via glycolysis and mitochondria-related pathway to regulate inflammatory pain
BACKGROUND: Dexamethasone (Dexa) has been recently found to exert an analgesic effect, whose action is closely related to IL-8. However, whether dexamethasone induces antinociception via glycolysis and mitochondria-related pathways is still unclear. METHODS: Right hind paw inflammatory pain in mice...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10506226/ https://www.ncbi.nlm.nih.gov/pubmed/37723417 http://dx.doi.org/10.1186/s12871-023-02277-9 |
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author | He, Ren Li, Xiaohan Zhang, Silun Liu, Yuqiang Xue, Qingsheng Luo, Yan Yu, Buwei Li, Xiongjuan Liu, Zhiheng |
author_facet | He, Ren Li, Xiaohan Zhang, Silun Liu, Yuqiang Xue, Qingsheng Luo, Yan Yu, Buwei Li, Xiongjuan Liu, Zhiheng |
author_sort | He, Ren |
collection | PubMed |
description | BACKGROUND: Dexamethasone (Dexa) has been recently found to exert an analgesic effect, whose action is closely related to IL-8. However, whether dexamethasone induces antinociception via glycolysis and mitochondria-related pathways is still unclear. METHODS: Right hind paw inflammatory pain in mice was induced by intraplantar injection of Freund’s Complete Adjuvant (FCA). Von Frey test was then used to measure the paw withdrawal threshold. The detection of glycolysis and mitochondrial pathway-related proteins and IL-8 were determined by Western blot and ELISA. The potential interaction between Dexa and fructose-1,6-bisphosphate (FBP, a PKM2 activator) was examined by simulation predictions using molecular docking. RESULTS: Intrathecal administration of Dexa (20 µg/20 µL) had an obvious analgesic effect in FCA-treated mice, which was counteracted by the glycolysis inhibitor 2-deoxyglucose (2-DG, 5 mg/20 µL) or the mitochondria-related pathway inhibitor oligomycin complex (Oligo, 5 µg/20 µL). In the glycolysis pathway, Dexa decreased GLUT3 and had no impact on HIF-1α expression during FCA-induced inflammation. Additionally, Dexa further increased the PKM2 level, accompanied by the formation of hydrogen bonds between Dexa and the PKM2 activator fructose-1,6-bisphosphate (FBP). In the mitochondrial pathway, Dexa downregulated the expression of Mfn2 protein but not the PGC-1α and SIRT-1 levels in the spinal cord. Moreover, both 2-DG and Oligo decreased Mfn2 expression. Finally, IL-8 level was reduced by the single or combined administration of Dexa, 2-DG, and Oligo. CONCLUSION: Dexa attenuated IL-8 expression via glycolysis and mitochondrial pathway-related proteins, thus mediating the analgesic effect during inflammatory pain. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12871-023-02277-9. |
format | Online Article Text |
id | pubmed-10506226 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-105062262023-09-19 Dexamethasone inhibits IL-8 via glycolysis and mitochondria-related pathway to regulate inflammatory pain He, Ren Li, Xiaohan Zhang, Silun Liu, Yuqiang Xue, Qingsheng Luo, Yan Yu, Buwei Li, Xiongjuan Liu, Zhiheng BMC Anesthesiol Research BACKGROUND: Dexamethasone (Dexa) has been recently found to exert an analgesic effect, whose action is closely related to IL-8. However, whether dexamethasone induces antinociception via glycolysis and mitochondria-related pathways is still unclear. METHODS: Right hind paw inflammatory pain in mice was induced by intraplantar injection of Freund’s Complete Adjuvant (FCA). Von Frey test was then used to measure the paw withdrawal threshold. The detection of glycolysis and mitochondrial pathway-related proteins and IL-8 were determined by Western blot and ELISA. The potential interaction between Dexa and fructose-1,6-bisphosphate (FBP, a PKM2 activator) was examined by simulation predictions using molecular docking. RESULTS: Intrathecal administration of Dexa (20 µg/20 µL) had an obvious analgesic effect in FCA-treated mice, which was counteracted by the glycolysis inhibitor 2-deoxyglucose (2-DG, 5 mg/20 µL) or the mitochondria-related pathway inhibitor oligomycin complex (Oligo, 5 µg/20 µL). In the glycolysis pathway, Dexa decreased GLUT3 and had no impact on HIF-1α expression during FCA-induced inflammation. Additionally, Dexa further increased the PKM2 level, accompanied by the formation of hydrogen bonds between Dexa and the PKM2 activator fructose-1,6-bisphosphate (FBP). In the mitochondrial pathway, Dexa downregulated the expression of Mfn2 protein but not the PGC-1α and SIRT-1 levels in the spinal cord. Moreover, both 2-DG and Oligo decreased Mfn2 expression. Finally, IL-8 level was reduced by the single or combined administration of Dexa, 2-DG, and Oligo. CONCLUSION: Dexa attenuated IL-8 expression via glycolysis and mitochondrial pathway-related proteins, thus mediating the analgesic effect during inflammatory pain. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12871-023-02277-9. BioMed Central 2023-09-18 /pmc/articles/PMC10506226/ /pubmed/37723417 http://dx.doi.org/10.1186/s12871-023-02277-9 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research He, Ren Li, Xiaohan Zhang, Silun Liu, Yuqiang Xue, Qingsheng Luo, Yan Yu, Buwei Li, Xiongjuan Liu, Zhiheng Dexamethasone inhibits IL-8 via glycolysis and mitochondria-related pathway to regulate inflammatory pain |
title | Dexamethasone inhibits IL-8 via glycolysis and mitochondria-related pathway to regulate inflammatory pain |
title_full | Dexamethasone inhibits IL-8 via glycolysis and mitochondria-related pathway to regulate inflammatory pain |
title_fullStr | Dexamethasone inhibits IL-8 via glycolysis and mitochondria-related pathway to regulate inflammatory pain |
title_full_unstemmed | Dexamethasone inhibits IL-8 via glycolysis and mitochondria-related pathway to regulate inflammatory pain |
title_short | Dexamethasone inhibits IL-8 via glycolysis and mitochondria-related pathway to regulate inflammatory pain |
title_sort | dexamethasone inhibits il-8 via glycolysis and mitochondria-related pathway to regulate inflammatory pain |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10506226/ https://www.ncbi.nlm.nih.gov/pubmed/37723417 http://dx.doi.org/10.1186/s12871-023-02277-9 |
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