miRNA-132-5p mediates a negative feedback regulation of IL-8 secretion through S100A8/A9 downregulation in neutrophil-like HL-60 cells



Zhou, Yang, Nomigni, Milène Tetsi, Gaigneaux, Anthoula, Tolle, Fabrice, Wright, Helen L ORCID: 0000-0003-0442-3134, Bueb, Jean-Luc and Bréchard, Sabrina
(2023) miRNA-132-5p mediates a negative feedback regulation of IL-8 secretion through S100A8/A9 downregulation in neutrophil-like HL-60 cells. Frontiers in Immunology, 14. 1274378-.

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Abstract

<jats:sec><jats:title>Background</jats:title><jats:p>Neutrophils are an important source of pro-inflammatory and immunomodulatory cytokines. This makes neutrophils efficient drivers of interactions with immune and non-immune cells to maintain homeostasis and modulate the inflammatory process by notably regulating the release of cytokines. Ca<jats:sup>2+</jats:sup>-dependent regulatory mechanism encompassing cytokine secretion by neutrophils are not still identified. In this context, we propose to define new insights on the role of Ca<jats:sup>2+</jats:sup>-binding proteins S100A8/A9 and on the regulatory role of miRNA-132-5p, which was identified as a regulator of S100A8/A9 expression, on IL-8 secretion.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Differentiated HL-60 cells, a human promyelocytic leukemia cell line that can be induced to differentiate into neutrophil-like cells, were used as a model of human neutrophils and treated with N- formyl-methionyl-leucyl-phenylalanine (fMLF), a bacterial peptide that activates neutrophils. shRNA knockdown was used to define the role of selected targets (S100A8/A9 and miRNA-132-5p) on IL-8 secretion.</jats:p></jats:sec><jats:sec><jats:title>Results and discussion</jats:title><jats:p>Different types of cytokines engage different signaling pathways in the secretion process. IL-8 release is tightly regulated by Ca<jats:sup>2+</jats:sup> binding proteins S100A8/A9. miRNA-132-5p is up-regulated over time upon fMLF stimulation and decreases S100A8/A9 expression and IL-8 secretion.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>These findings reveal a novel regulatory loop involving S100A8/A9 and miRNA-132-5p that modulates IL-8 secretion by neutrophils in inflammatory conditions. This loop could be a potential target for therapeutic intervention in inflammatory diseases.</jats:p></jats:sec>

Item Type: Article
Uncontrolled Keywords: Neutrophils, HL-60 Cells, Humans, Calgranulin A, Calgranulin B, MicroRNAs, Interleukin-8, Cytokines, Down-Regulation, Feedback
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User: Symplectic Admin
Date Deposited: 17 Jan 2024 09:35
Last Modified: 02 Feb 2024 14:34
DOI: 10.3389/fimmu.2023.1274378
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3177875