2-DG Re-Normalized IFN-γ Production in T Cells Excluding T<sub>EMRA</sub> Cells from Patients with Aplastic Anemia

Zhang, Yue; Zhang, Yuping; Chen, Xiaohui; Zhang, Yikai; Liu, Xiaoen; Wu, Shujuan; Li, Yangqiu; Li, Bo

doi:10.1080/08820139.2023.2195436

Cited by 1 publication

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“…Macrophages developed various protective mechanisms against their own During the metabolic switch of M1 polarized macrophages, mETC and OXPHOS become blocked [18,19] (Figure 1). To compensate for the energy loss, glucose is metabolized into lactate via aerobic glycolysis [20,21] (Figure 1A). One of the important reasons for metabolic reprogramming is to alter the role of mitochondria from ATP synthesis to ROS production [22].…”

Section: Introductionmentioning

confidence: 99%

Highly Selective MIF Ketonase Inhibitor KRP-6 Diminishes M1 Macrophage Polarization and Metabolic Reprogramming

Vámos,

Kálmán,

Sturm

et al. 2023

Antioxidants

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Macrophage polarization is highly involved in autoimmunity. M1 polarized macrophages drive inflammation and undergo metabolic reprogramming, involving downregulation of mitochondrial energy production and acceleration of glycolysis. Macrophage migration inhibitory factor (MIF), an enigmatic tautomerase (ketonase and enolase), was discovered to regulate M1 polarization. Here, we reveal that KRP-6, a potent and highly selective MIF ketonase inhibitor, reduces MIF-induced human blood eosinophil and neutrophil migration similarly to ISO-1, the most investigated tautomerase inhibitor. We equally discovered that KRP-6 prevents M1 macrophage polarization and reduces ROS production in IFN-γ-treated cells. During metabolic reprogramming, KRP-6 improved mitochondrial bioenergetics by ameliorating basal respiration, ATP production, coupling efficiency and maximal respiration in LPS+IFN-γ-treated cells. KRP-6 also reduced glycolytic flux in M1 macrophages. Moreover, the selective MIF ketonase inhibitor attenuated LPS+IFN-γ-induced downregulation of PARP-1 and PARP-2 mRNA expression. We conclude that KRP-6 represents a promising novel therapeutic compound for autoimmune diseases, which strongly involves M1 macrophage polarization.

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Section: Introductionmentioning

confidence: 99%

Highly Selective MIF Ketonase Inhibitor KRP-6 Diminishes M1 Macrophage Polarization and Metabolic Reprogramming

Vámos,

Kálmán,

Sturm

et al. 2023

Antioxidants

View full text Add to dashboard Cite

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2-DG Re-Normalized IFN-γ Production in T Cells Excluding T_EMRA Cells from Patients with Aplastic Anemia

Cited by 1 publication

References 45 publications

Highly Selective MIF Ketonase Inhibitor KRP-6 Diminishes M1 Macrophage Polarization and Metabolic Reprogramming

Highly Selective MIF Ketonase Inhibitor KRP-6 Diminishes M1 Macrophage Polarization and Metabolic Reprogramming

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2-DG Re-Normalized IFN-γ Production in T Cells Excluding TEMRA Cells from Patients with Aplastic Anemia

Cited by 1 publication

References 45 publications

Highly Selective MIF Ketonase Inhibitor KRP-6 Diminishes M1 Macrophage Polarization and Metabolic Reprogramming

Highly Selective MIF Ketonase Inhibitor KRP-6 Diminishes M1 Macrophage Polarization and Metabolic Reprogramming

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2-DG Re-Normalized IFN-γ Production in T Cells Excluding T_EMRA Cells from Patients with Aplastic Anemia