| Full text | |
| Author(s): Show less - |
Toller-Kawahisa, Juliana Escher
;
Viacava, Paula Ramos
;
Palsson-McDermott, Eva Margareta
;
Nascimento, Daniele Carvalho
;
Cervantes-Silva, Mariana Patricia
;
O'Carroll, Shane Myles
;
Zotta, Alessia
;
Damasceno, Luis Eduardo Alves
;
Publio, Gabriel Azevedo
;
Forti, Pedro
;
Luiz, Joao Paulo Mesquita
;
de Melo, Bruno Marcel Silva
;
Martins, Timna Varela
;
Faca, Vitor Marcel
;
Curtis, Annie
;
Cunha, Thiago Mattar
;
Cunha, Fernando de Queiroz
;
O'Neill, Luke Anthony John
;
Alves-Filho, Jose Carlos
Total Authors: 19
|
| Document type: | Journal article |
| Source: | CELL REPORTS; v. 44, n. 1, p. 15-pg., 2025-01-07. |
| Abstract | |
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 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. (AU) | |
| FAPESP's process: | 13/08216-2 - CRID - Center for Research in Inflammatory Diseases |
| Grantee: | Fernando de Queiroz Cunha |
| Support Opportunities: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |
| FAPESP's process: | 19/25298-9 - Role of PKM2 in neutrophil metabolism and function |
| Grantee: | Juliana Escher Toller |
| Support Opportunities: | Scholarships abroad - Research Internship - Post-doctor |
| FAPESP's process: | 17/01714-8 - PKM2 contribution to neutrophils' activation in experimental systemic lupus erythematosus onset |
| Grantee: | Juliana Escher Toller |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |