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MiRNA-132-5p Mediates a Negative Feedback Regulation of IL-8 Secretion Through S100A8/A9 Downregulation in Neutrophil-like HL-60 Cells

Overview
Journal Front Immunol
Date 2024 Jan 31
PMID 38292491
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Abstract

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-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-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 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.

Citing Articles

Unraveling the Mechanisms of S100A8/A9 in Myocardial Injury and Dysfunction.

Xu Y, Wang Y, Ning K, Bao Y Curr Issues Mol Biol. 2024; 46(9):9707-9720.

PMID: 39329929 PMC: 11429546. DOI: 10.3390/cimb46090577.

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