Sulforaphane diminishes moonlighting of pyruvate kinase M2 and interleukin 1β expression in M1 (LPS) macrophages.

Autor:	Bahiraii S; Department of Pharmaceutical Sciences, University of Vienna, Vienna, Austria.; Vienna Doctoral School of Pharmaceutical, Nutritional and Sport Sciences (VDS PhaNuSpo), University of Vienna, Vienna, Austria., Brenner M; Department of Pharmaceutical Sciences, University of Vienna, Vienna, Austria.; Vienna Doctoral School of Pharmaceutical, Nutritional and Sport Sciences (VDS PhaNuSpo), University of Vienna, Vienna, Austria.; Vienna Metabolomics Center (VIME), University of Vienna, Vienna, Austria., Yan F; Department of Pharmaceutical Sciences, University of Vienna, Vienna, Austria.; College of Food Science and Technology, Huazhong Agricultural University, Wuhan, China., Weckwerth W; Vienna Metabolomics Center (VIME), University of Vienna, Vienna, Austria.; Molecular Systems Biology (MOSYS), Department of Functional and Evolutionary Ecology, University of Vienna, Vienna, Austria., Heiss EH; Department of Pharmaceutical Sciences, University of Vienna, Vienna, Austria.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 Aug 02; Vol. 13, pp. 935692. Date of Electronic Publication: 2022 Aug 02 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.935692
Abstrakt:	Murine macrophages activated by the Toll-like receptor 4 agonist lipopolysaccharide (LPS) polarize to the M1 type by inducing proinflammatory marker proteins and changing their energy metabolism to increased aerobic glycolysis and reduced respiration. We here show that the aliphatic isothiocyanate sulforaphane (Sfn) diminishes M1 marker expression (IL-1β, IL-6, TNF-α, iNOS, NO, and ROS) and leads to highly energetic cells characterized by both high glycolytic and high respiratory activity as assessed by extracellular flux analysis. Focusing on a potential connection between high glycolytic activity and low IL-1β expression in M1 (LPS/Sfn) macrophages, we reveal that Sfn impedes the moonlighting function of pyruvate kinase M2 (PKM2) in M1 macrophages. Sfn limits mono/dimerization and nuclear residence of PKM2 accompanied by reduced HIF-1α levels, Stat3 phosphorylation at tyrosine 705, and IL-1β expression while preserving high levels of cytosolic PKM2 tetramer with high glycolytic enzyme activity. Sfn prevents glutathionylation of PKM2 in LPS-stimulated macrophages which may account for the reduced loss of PKM2 tetramer. Overall, we uncover PKM2 as a novel affected hub within the anti-inflammatory activity profile of Sfn. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Bahiraii, Brenner, Yan, Weckwerth and Heiss.)
Databáze:	MEDLINE
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