Anti-inflammatory effect of IL-10 mediated by metabolic reprogramming of macrophages
| Autor: | Dror S. Shouval, Ruslan Medzhitov, Scott B. Snapper, W. K. Eddie Ip, Namiko Hoshi |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Inflammasomes medicine.medical_treatment Interleukin-1beta Oxidative phosphorylation Biology Article Mice 03 medical and health sciences NLR Family Pyrin Domain-Containing 3 Protein Mitophagy medicine Animals Humans Receptors Interleukin-10 PI3K/AKT/mTOR pathway Inflammation Multidisciplinary DDIT4 TOR Serine-Threonine Kinases Macrophages Inflammasome Macrophage Activation Colitis Inflammatory Bowel Diseases Mice Mutant Strains Interleukin-10 Mitochondria Cell biology Intestines Disease Models Animal Interleukin 10 030104 developmental biology Cytokine Immunology biology.protein Signal transduction Reactive Oxygen Species Signal Transduction Transcription Factors medicine.drug |
| Zdroj: | Science. 356:513-519 |
| ISSN: | 1095-9203 0036-8075 |
| Popis: | Interleukin 10 (IL-10) is an anti-inflammatory cytokine that plays a critical role in the control of immune responses. However, its mechanisms of action remain poorly understood. Here, we show that IL-10 opposes the switch to the metabolic program induced by inflammatory stimuli in macrophages. Specifically, we show that IL-10 inhibits lipopolysaccharide-induced glucose uptake and glycolysis and promotes oxidative phosphorylation. Furthermore, IL-10 suppresses mammalian target of rapamycin (mTOR) activity through the induction of an mTOR inhibitor, DDIT4. Consequently, IL-10 promotes mitophagy that eliminates dysfunctional mitochondria characterized by low membrane potential and a high level of reactive oxygen species. In the absence of IL-10 signaling, macrophages accumulate damaged mitochondria in a mouse model of colitis and inflammatory bowel disease patients, and this results in dysregulated activation of the NLRP3 inflammasome and production of IL-1β. |
| Databáze: | OpenAIRE |
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