Dexamethasone has profound influence on the energy metabolism of porcine blood leukocytes and prevents the LPS-induced glycolytic switch
In farm animals, little is known about the relationship between energy metabolism of immune cells and their activation state. Moreover, there has recently been evidence that dexamethasone, a powerful glucocorticoid-based drug, can exert its anti-inflammatory effects by interfering with the energy me...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1514061/full |
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| author | Wenjuan Ma Julia Brenmoehl Nares Trakooljul Klaus Wimmers Eduard Murani |
| author_facet | Wenjuan Ma Julia Brenmoehl Nares Trakooljul Klaus Wimmers Eduard Murani |
| author_sort | Wenjuan Ma |
| collection | DOAJ |
| description | In farm animals, little is known about the relationship between energy metabolism of immune cells and their activation state. Moreover, there has recently been evidence that dexamethasone, a powerful glucocorticoid-based drug, can exert its anti-inflammatory effects by interfering with the energy metabolism of immune cells, but the mechanisms are not yet fully understood. To address these knowledge gaps, we explored the connection between the energy metabolism of porcine peripheral blood mononuclear cells (PBMCs) and their response to pro- and anti-inflammatory stimulation with lipopolysaccharide (LPS) and dexamethasone (DEX) in vitro. Interventions in the metabolism of PBMCs with the glycolysis inhibitor 2-deoxy-D-glucose or the HIF-1α inhibitor KC7F2 reduced the LPS-induced TNF-α production, but the mitochondrial ATP synthesis inhibitor oligomycin showed no significant effect. The anti-inflammatory action of DEX was not affected by any of the inhibitors. To investigate the metabolic actions of LPS and DEX in PBMCs, we evaluated glycolysis and mitochondrial respiration following 24 hours stimulation using the Seahorse XFe96 flux analyzer. Our results revealed significantly higher glycolysis in LPS-treated PBMCs, but provided no evidence for a change in mitochondrial respiration. In contrast, DEX reduced LPS-induced glycolysis and, especially when administered alone, significantly lowered mitochondrial respiration. Pretreatment with KC7F2 counteracted the effects of LPS and DEX on glycolysis, and reduced mitochondrial respiration regardless of the inflammatory state of the PBMCs. Gene expression analysis identified the glucose transporter SLC2A3, and the tricarboxylic acid cycle genes IDH1 and SDHB as the main switches for the antagonistic metabolic actions of LPS and DEX, which are closely associated with the inflammatory state of PBMCs. |
| format | Article |
| id | doaj-art-daeda0ee69164153a257f2cb65c01a10 |
| institution | DOAJ |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-daeda0ee69164153a257f2cb65c01a102025-08-20T03:11:17ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011610.3389/fimmu.2025.15140611514061Dexamethasone has profound influence on the energy metabolism of porcine blood leukocytes and prevents the LPS-induced glycolytic switchWenjuan Ma0Julia Brenmoehl1Nares Trakooljul2Klaus Wimmers3Eduard Murani4Working Group Physiological Genomics, Research Institute for Farm Animal Biology (FBN), Dummerstorf, GermanyWorking Group Endocrinology of Farm Animals, Research Institute for Farm Animal Biology (FBN), Dummerstorf, GermanyWorking Group Physiological Genomics, Research Institute for Farm Animal Biology (FBN), Dummerstorf, GermanyWorking Group Physiological Genomics, Research Institute for Farm Animal Biology (FBN), Dummerstorf, GermanyWorking Group Physiological Genomics, Research Institute for Farm Animal Biology (FBN), Dummerstorf, GermanyIn farm animals, little is known about the relationship between energy metabolism of immune cells and their activation state. Moreover, there has recently been evidence that dexamethasone, a powerful glucocorticoid-based drug, can exert its anti-inflammatory effects by interfering with the energy metabolism of immune cells, but the mechanisms are not yet fully understood. To address these knowledge gaps, we explored the connection between the energy metabolism of porcine peripheral blood mononuclear cells (PBMCs) and their response to pro- and anti-inflammatory stimulation with lipopolysaccharide (LPS) and dexamethasone (DEX) in vitro. Interventions in the metabolism of PBMCs with the glycolysis inhibitor 2-deoxy-D-glucose or the HIF-1α inhibitor KC7F2 reduced the LPS-induced TNF-α production, but the mitochondrial ATP synthesis inhibitor oligomycin showed no significant effect. The anti-inflammatory action of DEX was not affected by any of the inhibitors. To investigate the metabolic actions of LPS and DEX in PBMCs, we evaluated glycolysis and mitochondrial respiration following 24 hours stimulation using the Seahorse XFe96 flux analyzer. Our results revealed significantly higher glycolysis in LPS-treated PBMCs, but provided no evidence for a change in mitochondrial respiration. In contrast, DEX reduced LPS-induced glycolysis and, especially when administered alone, significantly lowered mitochondrial respiration. Pretreatment with KC7F2 counteracted the effects of LPS and DEX on glycolysis, and reduced mitochondrial respiration regardless of the inflammatory state of the PBMCs. Gene expression analysis identified the glucose transporter SLC2A3, and the tricarboxylic acid cycle genes IDH1 and SDHB as the main switches for the antagonistic metabolic actions of LPS and DEX, which are closely associated with the inflammatory state of PBMCs.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1514061/fullinflammationglucocorticoid receptorimmunometabolismPBMCdexamethasonelipopolysaccharide (LPS) |
| spellingShingle | Wenjuan Ma Julia Brenmoehl Nares Trakooljul Klaus Wimmers Eduard Murani Dexamethasone has profound influence on the energy metabolism of porcine blood leukocytes and prevents the LPS-induced glycolytic switch Frontiers in Immunology inflammation glucocorticoid receptor immunometabolism PBMC dexamethasone lipopolysaccharide (LPS) |
| title | Dexamethasone has profound influence on the energy metabolism of porcine blood leukocytes and prevents the LPS-induced glycolytic switch |
| title_full | Dexamethasone has profound influence on the energy metabolism of porcine blood leukocytes and prevents the LPS-induced glycolytic switch |
| title_fullStr | Dexamethasone has profound influence on the energy metabolism of porcine blood leukocytes and prevents the LPS-induced glycolytic switch |
| title_full_unstemmed | Dexamethasone has profound influence on the energy metabolism of porcine blood leukocytes and prevents the LPS-induced glycolytic switch |
| title_short | Dexamethasone has profound influence on the energy metabolism of porcine blood leukocytes and prevents the LPS-induced glycolytic switch |
| title_sort | dexamethasone has profound influence on the energy metabolism of porcine blood leukocytes and prevents the lps induced glycolytic switch |
| topic | inflammation glucocorticoid receptor immunometabolism PBMC dexamethasone lipopolysaccharide (LPS) |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1514061/full |
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