Article ; Online: Ghrelin effects on mitochondrial fitness modulates macrophage function.
Free radical biology & medicine
2019 Volume 145, Page(s) 61–66
Abstract: 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 ... ...
| Abstract | 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. |
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| MeSH term(s) | Adenosine Triphosphate/genetics ; Animals ; Gene Expression Regulation, Neoplastic/drug effects ; Ghrelin/chemistry ; Ghrelin/pharmacology ; Glycolysis/drug effects ; Inflammation/chemically induced ; Inflammation/drug therapy ; Inflammation/genetics ; Inflammation/pathology ; Interleukin-12/genetics ; Interleukin-1beta/genetics ; Lipopolysaccharides/toxicity ; Macrophages, Peritoneal/drug effects ; Macrophages, Peritoneal/pathology ; Membrane Potential, Mitochondrial/drug effects ; Mice ; Mitochondria/drug effects ; Mitochondria/ultrastructure ; Nitric Oxide/genetics ; Signal Transduction/genetics ; Tumor Necrosis Factor-alpha/genetics |
| Chemical Substances | Ghrelin ; IL1B protein, mouse ; Interleukin-1beta ; Lipopolysaccharides ; Tumor Necrosis Factor-alpha ; Interleukin-12 (187348-17-0) ; Nitric Oxide (31C4KY9ESH) ; Adenosine Triphosphate (8L70Q75FXE) |
| Language | English |
| Publishing date | 2019-09-14 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 807032-5 |
| ISSN | 1873-4596 ; 0891-5849 |
| ISSN (online) | 1873-4596 |
| ISSN | 0891-5849 |
| DOI | 10.1016/j.freeradbiomed.2019.09.012 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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