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miRNAs Regulate Cytokine Secretion Induced by Phosphorylated S100A8/A9 in Neutrophils

Immune Cells and Inflammatory Diseases group, Life Sciences Research Unit, University of Luxembourg, L-4367 Belvaux, Luxembourg
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Int. J. Mol. Sci. 2019, 20(22), 5699; https://doi.org/10.3390/ijms20225699
Received: 3 October 2019 / Revised: 6 November 2019 / Accepted: 12 November 2019 / Published: 14 November 2019
(This article belongs to the Section Molecular Immunology)
The release of cytokines by neutrophils constitutes an essential process in the development of inflammation by recruiting and activating additional cells. Neutrophils are also able to secrete a complex of S100A8 and S100A9 proteins (S100A8/A9), which can amplify the general inflammatory state of the host and is involved in the pathogenesis of several chronic inflammatory diseases, such as rheumatoid arthritis (RA). S100A8/A9 have received renewed attention due to their susceptibility to several function-altering post-translational modifications. In that context, it has been recently demonstrated that only the phosphorylated form of S100A8/A9 (S100A8/A9-P) is able to induce the secretion of several cytokines in neutrophils. Here, we investigate the mechanism by which this post-translational modification of S100A8/A9 can regulate the extracellular activity of the protein complex and its impact on the inflammatory functions of neutrophils. We found that S100A8/A9-P are present in large amounts in the synovial fluids from RA patients, highlighting the importance of this form of S100A8/A9 complex in the inflammation process. Using miRNA-sequencing on S100A8/A9-P-stimulated differentiated HL-60 cells, we identified a dysregulation of miR-146a-5p and miR-155-5p expression through TRL4 signaling pathways. Our data reveal that overexpression of these miRNAs in neutrophil-like cells reduces S100A8/A9-P-mediated secretion of pro-inflammatory cytokines. View Full-Text
Keywords: miRNAs; cytokines; inflammation; S100A8/A9; neutrophils miRNAs; cytokines; inflammation; S100A8/A9; neutrophils
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MDPI and ACS Style

Jung, N.; Schenten, V.; Bueb, J.-L.; Tolle, F.; Bréchard, S. miRNAs Regulate Cytokine Secretion Induced by Phosphorylated S100A8/A9 in Neutrophils. Int. J. Mol. Sci. 2019, 20, 5699.

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