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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. | LitMetric

AI Article Synopsis

  • Neutrophils play a key role in inflammation by releasing cytokines, but the specific mechanisms regulating this process, especially those involving calcium (Ca) signaling, are not fully understood.
  • Researchers investigated how Ca-binding proteins S100A8/A9 and the microRNA miRNA-132-5p affect the secretion of IL-8, an important inflammatory cytokine, in a model using human neutrophil-like cells.
  • The study found that S100A8/A9 proteins regulate IL-8 release and that miRNA-132-5p, which is activated during inflammation, negatively impacts S100A8/A9 expression and IL-8 secretion, suggesting this regulatory loop could be targeted for treating inflammatory diseases.

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10824955PMC
http://dx.doi.org/10.3389/fimmu.2023.1274378DOI Listing

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