Sphingolipid metabolism during Toll-like receptor 4 (TLR4)-mediated macrophage activation - PubMed (original) (raw)

Review

. 2021 Dec;178(23):4575-4587.

doi: 10.1111/bph.15642. Epub 2021 Sep 2.

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Review

Sphingolipid metabolism during Toll-like receptor 4 (TLR4)-mediated macrophage activation

Antoni Olona et al. Br J Pharmacol. 2021 Dec.

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Abstract

Macrophage activation in response to stimulation of Toll-like receptor 4 (TLR4) provides a paradigm for investigating energy metabolism that regulates the inflammatory response. TLR4-mediated pro-inflammatory macrophage activation is characterized by increased glycolysis and altered mitochondrial metabolism, supported by selective amino acid uptake and/or usage. Fatty acid metabolism remains as a highly complex rewiring that accompanies classical macrophage activation. TLR4 activation leads to de novo synthesis of fatty acids, which flux into sphingolipids, complex lipids that form the building blocks of eukaryotic cell membranes and regulate cell function. Here, we review the importance of TLR4-mediated de novo synthesis of membrane sphingolipids in macrophages. We first highlight fatty acid metabolism during TLR4-driven macrophage immunometabolism. We then focus on the temporal dynamics of sphingolipid biosynthesis and emphasize the modulatory role of some sphingolipid species (i.e. sphingomyelins, ceramides and glycosphingolipids) on the pro-inflammatory and pro-resolution phases of LPS/TLR4 activation in macrophages.

Keywords: LPS; TLR4; fatty acid metabolism; lipidomics; macrophages; sphingolipids.

© 2021 The British Pharmacological Society.

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References

REFERENCES

    1. Abuawad, A., Mbadugha, C., Ghaemmaghami, A. M., & Kim, D. H. (2020). Metabolic characterisation of THP-1 macrophage polarisation using LC-MS-based metabolite profiling. Metabolomics, 16, 33. https://doi.org/10.1007/s11306-020-01656-4
    1. Aderem, A., & Ulevitch, R. J. (2000). Toll-like receptors in the induction of the innate immune response. Nature, 406, 782-787. https://doi.org/10.1038/35021228
    1. Aerts, J., Artola, M., van Eijk, M., Ferraz, M. J., & Boot, R. G. (2019). Glycosphingolipids and infection. Potential new therapeutic avenues. Frontiers in Cell and Developmental Biology, 7, 324.
    1. Alexander, S. P. H., Christopoulos, A., Davenport, A. P., Kelly, E., Mathie, A., Peters, J. A., Veale, E. L., Armstrong, J. F., Faccenda, E., Harding, S. D., & Pawson, A. J. (2019). The Concise Guide to PHARMACOLOGY 2019/20: G protein-coupled receptors. British Journal of Pharmacology, 176(Suppl 1), S21-S141.
    1. Al-Rashed, F., Ahmad, Z., Thomas, R., Melhem, M., Snider, A. J., Obeid, L. M., Al-Mulla, F., Hannun, Y. A., & Ahmad, R. (2020). Neutral sphingomyelinase 2 regulates inflammatory responses in monocytes/macrophages induced by TNF-α. Scientific Reports, 10, 16802. https://doi.org/10.1038/s41598-020-73912-5

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