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SHR Neuro Cancer Cardio Lipid Metab Microb

Zotta, A; Toller-Kawahisa, J; Palsson-McDermott, EM; O'Carroll, SM; Henry, ÓC; Day, EA; McGettrick, AF; Ward, RW; Ryan, DG; Watson, MA; Brand, MD; Runtsch, MC; Maitz, K; Lueger, A; Kargl, J; Miljkovic, JL; Lavelle, EC; O'Neill, LAJ.
Mitochondrial respiratory complex III sustains IL-10 production in activated macrophages and promotes tumor-mediated immune evasion.
Sci Adv. 2025; 11(4):eadq7307 Doi: 10.1126/sciadv.adq7307 [OPEN ACCESS]
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Co-authors Med Uni Graz: Kargl Julia; Lueger Anna; Maitz Kathrin; Runtsch Marah
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Abstract:: The cytokine interleukin-10 (IL-10) limits the immune response and promotes resolution of acute inflammation. Because of its immunosuppressive effects, IL-10 up-regulation is a common feature of tumor progression and metastasis. Recently, IL-10 regulation has been shown to depend on mitochondria and redox-sensitive signals. We have found that Suppressor of site III_Qo Electron Leak 1.2 (S3QEL 1.2), a specific inhibitor of reactive oxygen species (ROS) production from mitochondrial complex III, and myxothiazol, a complex III inhibitor, decrease IL-10 in lipopolysaccharide (LPS)-activated macrophages. IL-10 down-regulation is likely to be mediated by suppression of c-Fos, which is a subunit of activator protein 1 (AP1), a transcription factor required for IL-10 gene expression. S3QEL 1.2 impairs IL-10 production in vivo after LPS challenge and promotes the survival of mice bearing B16F10 melanoma by lowering tumor growth. Our data identify a link between complex III-dependent ROS generation and IL-10 production in macrophages, the targeting of which could have potential in boosting antitumor immunity.
Find related publications in this database (using NLM MeSH Indexing): Interleukin-10 - metabolism; Animals - administration & dosage; Macrophages - metabolism, immunology; Mice - administration & dosage; Reactive Oxygen Species - metabolism; Mitochondria - metabolism; Macrophage Activation - administration & dosage; Electron Transport Complex III - metabolism; Melanoma, Experimental - metabolism, immunology, pathology; Lipopolysaccharides - pharmacology; Tumor Escape - administration & dosage; Mice, Inbred C57BL - administration & dosage; Humans - administration & dosage