ADP-dependent glucokinase (ADPGK) is not critical for the activation of human macrophages by LPS-Immunometabolism-CSCIED科技核心评价数据库-手机版

ADP-dependent glucokinase (ADPGK) is not critical for the activation of human macrophages by LPS

ADP-dependent glucokinase (ADPGK) is not critical for the activation of human macrophages by LPS

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DOI	10.1097/IN9.0000000000000006
刊名	Immunometabolism IJ
年，卷(期)	2022, 4(3)
作者	Geiger, Benjamin; Wang, Bei-Tzu; Munteanu, Bogdan; Riedel, Jens; Zezina, Ekaterina; Biesemann, Nadine; Schmoll, Dieter,
作者单位	[Geiger, Benjamin; Zezina, Ekaterina; Biesemann, Nadine; Schmoll, Dieter] Sanofi R&D, TA Immunol, Ind pk Hoechst, Frankfurt, Germany; [Wang, Bei-Tzu; Munteanu, Bogdan; Riedel, Jens] Sanofi R&D, Drug Metab & Pharmacokinet, Metab Imaging Mass Spectrometry G
摘要	Background:Activated immune cells show an enhanced glucose metabolism, suggesting that the inhibition of this pathway selective in immune cells could be a potential approach to combat inflammatory diseases. We studied here whether ADP-dependent glucokinase (ADPGK), a glucose-phosphorylating enzyme predominantly expressed in immune cells, could be a suitable target for the inhibition of macrophage activation.Methods:The regulation and role of ADPGK in human primary macrophages differentiated from blood monocytes was studied using Real-time quantitative PCR (RT-qPCR), gene silencing, whole-cell MALDI-mass spectrometry (MS) imaging as well as immune-based and enzymatic medium analyzes.Results:The expression of ADPGK was induced in response to the activation of toll-like receptors (TLRs). The most robust effect was observed with the TLR4 ligand Lipopolysaccharide (LPS) leading to an approximately 4-fold increase of ADPGK RNA levels. For this induction, the activation of p38 MAPK and IKK epsilon was important. Silencing of ADPGK expression using siRNAs had neither an effect on LPS-induced expression and release of proinflammatory cytokines nor on cellular ATP levels and lactate production. Untargeted metabolic cell profiling by whole-cell MALDI-MS imaging did not reveal any metabolic regulations after ADPGK down-regulation suggesting no specific metabolic pathway involvement.Conclusions:ADPGK neither catalyzes a rate-limiting step of glucose metabolism in LPS-activated macrophages nor is required for the proinflammatory phenotype of these cells in vitro. Our data do not indicate that ADPGK inhibition could be a pharmacological approach to modulate immunometabolism.
Abstract	Background:Activated immune cells show an enhanced glucose metabolism, suggesting that the inhibition of this pathway selective in immune cells could be a potential approach to combat inflammatory diseases. We studied here whether ADP-dependent glucokinase (ADPGK), a glucose-phosphorylating enzyme predominantly expressed in immune cells, could be a suitable target for the inhibition of macrophage activation.Methods:The regulation and role of ADPGK in human primary macrophages differentiated from blood monocytes was studied using Real-time quantitative PCR (RT-qPCR), gene silencing, whole-cell MALDI-mass spectrometry (MS) imaging as well as immune-based and enzymatic medium analyzes.Results:The expression of ADPGK was induced in response to the activation of toll-like receptors (TLRs). The most robust effect was observed with the TLR4 ligand Lipopolysaccharide (LPS) leading to an approximately 4-fold increase of ADPGK RNA levels. For this induction, the activation of p38 MAPK and IKK epsilon was important. Silencing of ADPGK expression using siRNAs had neither an effect on LPS-induced expression and release of proinflammatory cytokines nor on cellular ATP levels and lactate production. Untargeted metabolic cell profiling by whole-cell MALDI-MS imaging did not reveal any metabolic regulations after ADPGK down-regulation suggesting no specific metabolic pathway involvement.Conclusions:ADPGK neither catalyzes a rate-limiting step of glucose metabolism in LPS-activated macrophages nor is required for the proinflammatory phenotype of these cells in vitro. Our data do not indicate that ADPGK inhibition could be a pharmacological approach to modulate immunometabolism.
关键词	inflammation; immunity; glucose; macrophages; hexokinase; energy metabolism
KeyWord	inflammation; immunity; glucose; macrophages; hexokinase; energy metabolism
基金项目
页码	1-10

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Geiger, Benjamin; Wang, Bei-Tzu; Munteanu, Bogdan; Riedel, Jens; Zezina, Ekaterina; Biesemann, Nadine; Schmoll, Dieter. ADP-dependent glucokinase (ADPGK) is not critical for the activation of human macrophages by LPS [J]. Immunometabolism. 2022; 4; (3). 1 - 10.

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