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

Front Immunol. 2024 Jan 16:14:1274378. doi: 10.3389/fimmu.2023.1274378. eCollection 2023.

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. Ca2+-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 Ca2+-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 Ca2+ 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.

Keywords: Ca2+ signaling; S100A8/A9; cytokines; inflammation; miRNA; neutrophils.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calgranulin A / genetics
  • Calgranulin A / metabolism
  • Calgranulin B / genetics
  • Calgranulin B / metabolism
  • Cytokines / metabolism
  • Down-Regulation
  • Feedback
  • HL-60 Cells
  • Humans
  • Interleukin-8 / metabolism
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Neutrophils*

Substances

  • Calgranulin B
  • Interleukin-8
  • Calgranulin A
  • Cytokines
  • MicroRNAs
  • MIRN132 microRNA, human

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the University of Luxembourg and the Fonds National de la Recherche through the PRIDE/11012546/NEXTIMMUNE FNR-PRIDE Doctoral Training Unit. HW was funded by a Versus Arthritis Career Development Fellowship (No. 21430).