miRNA-132-5p mediates a negative feedback regulation of IL-8 secretion through S100A8/A9 downregulation in neutrophil-like HL-60 cells.
Autor: | Zhou Y; Department of Life Sciences and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg., Nomigni MT; Department of Life Sciences and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg., Gaigneaux A; Department of Life Sciences and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg., Tolle F; Department of Life Sciences and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg., Wright HL; Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, United Kingdom., Bueb JL; Department of Life Sciences and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg., Bréchard S; Department of Life Sciences and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg. |
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Jazyk: | angličtina |
Zdroj: | Frontiers in immunology [Front Immunol] 2024 Jan 16; Vol. 14, pp. 1274378. Date of Electronic Publication: 2024 Jan 16 (Print Publication: 2023). |
DOI: | 10.3389/fimmu.2023.1274378 |
Abstrakt: | Background: 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 2+ -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 2+ -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. Methods: 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. Results and Discussion: Different types of cytokines engage different signaling pathways in the secretion process. IL-8 release is tightly regulated by Ca 2+ binding proteins S100A8/A9. miRNA-132-5p is up-regulated over time upon fMLF stimulation and decreases S100A8/A9 expression and IL-8 secretion. Conclusion: 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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Zhou, Nomigni, Gaigneaux, Tolle, Wright, Bueb and Bréchard.) |
Databáze: | MEDLINE |
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