Modelling Microglial Innate Immune Memory In Vitro: Understanding the Role of Aerobic Glycolysis in Innate Immune Memory
Abstract
:1. Introduction
2. Results
2.1. Two Hits of LPS Produce Tolerance In Vitro
2.1.1. Two Hits of LPS Result in Attenuation of Inflammatory Gene Expression
2.1.2. Two Hits of LPS Result in Attenuation of Microglial Phagocytosis and NO Release
2.2. BAFF Pre-Treatment Produces Training In Vitro
2.2.1. BAFF Pre-Treatment Results in Excessive Induction of Inflammatory Gene Expression upon LPS Stimulus
2.2.2. BAFF Pre-Treatment Results in Excessive Induction of Phagocytosis and NO Release
2.3. LPS but Not BAFF Results in Rapid Changes in Cellular Metabolism and Induction of Aerobic Glycolysis
2.4. Inhibition of LPS-Induced Aerobic Glycolysis Impairs Establishment of Microglial Memory
2.4.1. Sodium Oxamate Attenuates LPS-Induced Gene Expression and Blocks Lactate Production
2.4.2. Treatment of Sodium Oxamate during the First Stimulus Blocks Establishment of the Tolerance Memory State Gene Expression but Not the Training Memory State
2.4.3. Sodium Oxamate Rescues Attenuation of Phagocytosis and NO Production
2.5. Tolerized Microglial Metabolic State Is Rescued by Sodium Oxamate Treatment during the First Hit
2.5.1. Two Hit of LPS Block Aerobic Glycolysis, whereas BAFF Pre-Treatment Enhances Aerobic Glycolysis
2.5.2. Sodium Oxamate Treatment Prevents the Tolerance-Induced Metabolic State
3. Discussion
4. Materials and Methods
4.1. BV2 Microglial Culture + Treatments
4.2. RNA-Extraction and RT-qPCR Analysis
4.3. pHrodo E. coli Phagocytosis Assay Quantified by Flow Cytometry
4.4. Griess Reagent Assay
4.5. Lactate Assay
4.6. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Target Gene | Forward Sequence (5′→3′) | Reverse Sequence (5′→3′) |
---|---|---|
Hprt | CAGTACAGCCCCAAAATGGTTA | AGTCTGGCCTGTATCCAACA |
Il1b | TGGCAACTGTTCCTGAACTCA | GGGTCCGTCAACTTCAAAGAAC |
Il6 | CGATGATGCACTTGCAGAAA | ACTCCAGAAGACCAGAGGAA |
Cxcl16 | ATCAGGTTCCAGTTGCAGTC | TTCCCATGACCAGTTCCAC |
Il10 | ACAAAGGACCAGCTGGACAA | TAAGGCTTGGCAACCCAAGTA |
Tnfa | GGGTGATCGGTCCCCAAA | TGAGGGTCTGGGCCATAGAA |
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Towriss, M.; MacVicar, B.; Ciernia, A.V. Modelling Microglial Innate Immune Memory In Vitro: Understanding the Role of Aerobic Glycolysis in Innate Immune Memory. Int. J. Mol. Sci. 2023, 24, 8967. https://doi.org/10.3390/ijms24108967
Towriss M, MacVicar B, Ciernia AV. Modelling Microglial Innate Immune Memory In Vitro: Understanding the Role of Aerobic Glycolysis in Innate Immune Memory. International Journal of Molecular Sciences. 2023; 24(10):8967. https://doi.org/10.3390/ijms24108967
Chicago/Turabian StyleTowriss, Morgan, Brian MacVicar, and Annie Vogel Ciernia. 2023. "Modelling Microglial Innate Immune Memory In Vitro: Understanding the Role of Aerobic Glycolysis in Innate Immune Memory" International Journal of Molecular Sciences 24, no. 10: 8967. https://doi.org/10.3390/ijms24108967
APA StyleTowriss, M., MacVicar, B., & Ciernia, A. V. (2023). Modelling Microglial Innate Immune Memory In Vitro: Understanding the Role of Aerobic Glycolysis in Innate Immune Memory. International Journal of Molecular Sciences, 24(10), 8967. https://doi.org/10.3390/ijms24108967