Ghrelin effects on mitochondrial fitness modulates macrophage function
| Autor: | Leonardo Pimentel de Freitas, Felipe Corrêa da Silva, Ana Campos Codo, Hernandes F. Carvalho, Aline Siqueira Berti, Gustavo Gastão Davanzo, Bianca Gazieri Castelucci, Sílvio Roberto Consonni, Pedro M. Moraes-Vieira, Danilo Lopes Ferrucci, Jessica Aparecida da Silva Pereira, Cristhiane Favero de Aguiar, Lauar de Brito Monteiro |
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| Rok vydání: | 2019 |
| Předmět: |
Lipopolysaccharides
0301 basic medicine medicine.medical_specialty Interleukin-1beta Pyruvate transport Enteroendocrine cell Mitochondrion Nitric Oxide Biochemistry Mice 03 medical and health sciences Adenosine Triphosphate 0302 clinical medicine Physiology (medical) Orexigenic Internal medicine medicine Animals Macrophage Secretion Glycolysis Inflammation Membrane Potential Mitochondrial Tumor Necrosis Factor-alpha Chemistry digestive oral and skin physiology Interleukin-12 Ghrelin Mitochondria Gene Expression Regulation Neoplastic 030104 developmental biology Endocrinology Macrophages Peritoneal hormones hormone substitutes and hormone antagonists 030217 neurology & neurosurgery Signal Transduction medicine.drug |
| Zdroj: | Free Radical Biology and Medicine. 145:61-66 |
| ISSN: | 0891-5849 |
| Popis: | Over the past years, systemic derived cues that regulate cellular metabolism have been implicated in the regulation of immune responses. Ghrelin is an orexigenic hormone produced by enteroendocrine cells in the gastric mucosa with known immunoregulatory roles. The mechanism behind the function of ghrelin in immune cells, such as macrophages, is still poorly understood. Here, we explored the hypothesis that ghrelin leads to alterations in macrophage metabolism thus modulating macrophage function. We demonstrated that ghrelin exerts an immunomodulatory effect over LPS-activated peritoneal macrophages, as evidenced by inhibition of TNF-α and IL-1β secretion and increased IL-12 production. Concomitantly, ghrelin increased mitochondrial membrane potential and increased respiratory rate. In agreement, ghrelin prevented LPS-induced ultrastructural damage in the mitochondria. Ghrelin also blunted LPS-induced glycolysis. In LPS-activated macrophages, glucose deprivation did not affect ghrelin-induced IL-12 secretion, whereas the inhibition of pyruvate transport and mitochondria-derived ATP abolished ghrelin-induced IL-12 secretion, indicating a dependence on mitochondrial function. Ghrelin pre-treatment of metabolic activated macrophages inhibited the secretion of TNF-α and enhanced IL-12 levels. Moreover, ghrelin effects on IL-12, and not on TNF-α, are dependent on mitochondria elongation, since ghrelin did not enhance IL-12 secretion in metabolic activated mitofusin-2 deficient macrophages. Thus, ghrelin affects macrophage mitochondrial metabolism and the subsequent macrophage function. |
| Databáze: | OpenAIRE |
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