Metabolic reprogramming of macrophages by PKM2 promotes IL-10 production via adenosine
Summary: Macrophages play a crucial role in immune responses and undergo metabolic reprogramming to fulfill their functions. The tetramerization of the glycolytic enzyme pyruvate kinase M2 (PKM2) induces the production of the anti-inflammatory cytokine interleukin (IL)-10 in vivo, but the underlying...
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| Language: | English |
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Elsevier
2025-01-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724015237 |
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| author | Juliana Escher Toller-Kawahisa Paula Ramos Viacava Eva Margareta Palsson-McDermott Daniele Carvalho Nascimento Mariana Patricia Cervantes-Silva Shane Myles O'Carroll Alessia Zotta Luis Eduardo Alves Damasceno Gabriel Azevedo Públio Pedro Forti João Paulo Mesquita Luiz Bruno Marcel Silva de Melo Timna Varela Martins Vitor Marcel Faça Annie Curtis Thiago Mattar Cunha Fernando de Queiroz Cunha Luke Anthony John O'Neill José Carlos Alves-Filho |
| author_facet | Juliana Escher Toller-Kawahisa Paula Ramos Viacava Eva Margareta Palsson-McDermott Daniele Carvalho Nascimento Mariana Patricia Cervantes-Silva Shane Myles O'Carroll Alessia Zotta Luis Eduardo Alves Damasceno Gabriel Azevedo Públio Pedro Forti João Paulo Mesquita Luiz Bruno Marcel Silva de Melo Timna Varela Martins Vitor Marcel Faça Annie Curtis Thiago Mattar Cunha Fernando de Queiroz Cunha Luke Anthony John O'Neill José Carlos Alves-Filho |
| author_sort | Juliana Escher Toller-Kawahisa |
| collection | DOAJ |
| description | Summary: Macrophages play a crucial role in immune responses and undergo metabolic reprogramming to fulfill their functions. The tetramerization of the glycolytic enzyme pyruvate kinase M2 (PKM2) induces the production of the anti-inflammatory cytokine interleukin (IL)-10 in vivo, but the underlying mechanism remains elusive. Here, we report that PKM2 activation with the pharmacological agent TEPP-46 increases IL-10 production in LPS-activated macrophages by metabolic reprogramming, leading to the production and release of ATP from glycolysis. The effect of TEPP-46 is abolished in PKM2-deficient macrophages. Extracellular ATP is converted into adenosine by ectonucleotidases that activate adenosine receptor A2a (A2aR) to enhance IL-10 production. Interestingly, IL-10 production induced by PKM2 activation is associated with improved mitochondrial health. Our results identify adenosine derived from glycolytic ATP as a driver of IL-10 production, highlighting the role of tetrameric PKM2 in regulating glycolysis to promote IL-10 production. |
| format | Article |
| id | doaj-art-53ed888fbb324ff0947e04fba28e0678 |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-53ed888fbb324ff0947e04fba28e06782025-01-09T06:13:49ZengElsevierCell Reports2211-12472025-01-01441115172Metabolic reprogramming of macrophages by PKM2 promotes IL-10 production via adenosineJuliana Escher Toller-Kawahisa0Paula Ramos Viacava1Eva Margareta Palsson-McDermott2Daniele Carvalho Nascimento3Mariana Patricia Cervantes-Silva4Shane Myles O'Carroll5Alessia Zotta6Luis Eduardo Alves Damasceno7Gabriel Azevedo Públio8Pedro Forti9João Paulo Mesquita Luiz10Bruno Marcel Silva de Melo11Timna Varela Martins12Vitor Marcel Faça13Annie Curtis14Thiago Mattar Cunha15Fernando de Queiroz Cunha16Luke Anthony John O'Neill17José Carlos Alves-Filho18Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil; Center for Research in Inflammatory Diseases, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil; School of Biochemistry and Immunology, Trinity Biomedical Science Institute, Trinity College Dublin, Dublin, IrelandDepartment of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil; Center for Research in Inflammatory Diseases, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, BrazilSchool of Biochemistry and Immunology, Trinity Biomedical Science Institute, Trinity College Dublin, Dublin, IrelandDepartment of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil; Center for Research in Inflammatory Diseases, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, BrazilSchool of Pharmacy and Biomolecular Sciences and Tissue Engineering Research Group, Royal College of Surgeons in Ireland, Dublin, IrelandSchool of Biochemistry and Immunology, Trinity Biomedical Science Institute, Trinity College Dublin, Dublin, IrelandSchool of Biochemistry and Immunology, Trinity Biomedical Science Institute, Trinity College Dublin, Dublin, IrelandDepartment of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil; Center for Research in Inflammatory Diseases, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, BrazilDepartment of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil; Center for Research in Inflammatory Diseases, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, BrazilDepartment of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil; Center for Research in Inflammatory Diseases, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, BrazilDepartment of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil; Center for Research in Inflammatory Diseases, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, BrazilDepartment of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil; Center for Research in Inflammatory Diseases, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, BrazilDepartment of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil; Center for Research in Inflammatory Diseases, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, BrazilDepartment of Biochemistry and Immunology, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, BrazilSchool of Pharmacy and Biomolecular Sciences and Tissue Engineering Research Group, Royal College of Surgeons in Ireland, Dublin, IrelandDepartment of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil; Center for Research in Inflammatory Diseases, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, BrazilDepartment of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil; Center for Research in Inflammatory Diseases, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, BrazilSchool of Biochemistry and Immunology, Trinity Biomedical Science Institute, Trinity College Dublin, Dublin, Ireland; Corresponding authorDepartment of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil; Center for Research in Inflammatory Diseases, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil; Corresponding authorSummary: Macrophages play a crucial role in immune responses and undergo metabolic reprogramming to fulfill their functions. The tetramerization of the glycolytic enzyme pyruvate kinase M2 (PKM2) induces the production of the anti-inflammatory cytokine interleukin (IL)-10 in vivo, but the underlying mechanism remains elusive. Here, we report that PKM2 activation with the pharmacological agent TEPP-46 increases IL-10 production in LPS-activated macrophages by metabolic reprogramming, leading to the production and release of ATP from glycolysis. The effect of TEPP-46 is abolished in PKM2-deficient macrophages. Extracellular ATP is converted into adenosine by ectonucleotidases that activate adenosine receptor A2a (A2aR) to enhance IL-10 production. Interestingly, IL-10 production induced by PKM2 activation is associated with improved mitochondrial health. Our results identify adenosine derived from glycolytic ATP as a driver of IL-10 production, highlighting the role of tetrameric PKM2 in regulating glycolysis to promote IL-10 production.http://www.sciencedirect.com/science/article/pii/S2211124724015237CP: ImmunologyCP: Metabolism |
| spellingShingle | Juliana Escher Toller-Kawahisa Paula Ramos Viacava Eva Margareta Palsson-McDermott Daniele Carvalho Nascimento Mariana Patricia Cervantes-Silva Shane Myles O'Carroll Alessia Zotta Luis Eduardo Alves Damasceno Gabriel Azevedo Públio Pedro Forti João Paulo Mesquita Luiz Bruno Marcel Silva de Melo Timna Varela Martins Vitor Marcel Faça Annie Curtis Thiago Mattar Cunha Fernando de Queiroz Cunha Luke Anthony John O'Neill José Carlos Alves-Filho Metabolic reprogramming of macrophages by PKM2 promotes IL-10 production via adenosine Cell Reports CP: Immunology CP: Metabolism |
| title | Metabolic reprogramming of macrophages by PKM2 promotes IL-10 production via adenosine |
| title_full | Metabolic reprogramming of macrophages by PKM2 promotes IL-10 production via adenosine |
| title_fullStr | Metabolic reprogramming of macrophages by PKM2 promotes IL-10 production via adenosine |
| title_full_unstemmed | Metabolic reprogramming of macrophages by PKM2 promotes IL-10 production via adenosine |
| title_short | Metabolic reprogramming of macrophages by PKM2 promotes IL-10 production via adenosine |
| title_sort | metabolic reprogramming of macrophages by pkm2 promotes il 10 production via adenosine |
| topic | CP: Immunology CP: Metabolism |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724015237 |
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