Neutrophil extracellular trap-enriched supernatants carry microRNAs able to modulate TNF-α production by macrophages

Sci Rep. 2020 Feb 17;10(1):2715. doi: 10.1038/s41598-020-59486-2.

Abstract

Neutrophil extracellular traps (NETs) emerge from the cell as a DNA scaffold associated with cytoplasmic and granular proteins, able to immobilize and kill pathogens. This association occurs following nuclear and granular membrane disintegration, allowing contact with the decondensed chromatin. Thus, it is reasonable to speculate that the DNA can also mix with miRNAs and carry them in NETs. Here, we report for the first time the presence of the miRNA carriers associated with NETs and miRNAs present in NET-enriched supernatants (NET-miRs), thus adding a novel class of molecules and new proteins that can be released and transported in the NET platform. We observed that the majority of NET-miRs were common to all four stimuli used (PMA, interleukin-8, amyloid fibrils and Leishmania), and that miRNA-142-3p carried by NETs down-modulates protein kinase Cα and regulates TNF-α production in macrophages upon NET interaction with these cells. Our findings unveil a novel role for NETs in the cell communication processes, allowing the conveyance of miRNA from neutrophils to neighboring cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid / pharmacology
  • Antagomirs / genetics
  • Antagomirs / metabolism
  • Cell Communication / immunology*
  • Culture Media, Conditioned / pharmacology
  • Extracellular Traps / immunology*
  • Extracellular Traps / metabolism
  • Gene Expression Regulation
  • Humans
  • Interleukin-8 / pharmacology
  • Leishmania braziliensis
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • MicroRNAs / immunology
  • Neutrophils / drug effects
  • Neutrophils / immunology*
  • Neutrophils / microbiology
  • Primary Cell Culture
  • Protein Kinase C-alpha / genetics
  • Protein Kinase C-alpha / immunology
  • Signal Transduction
  • THP-1 Cells
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tumor Necrosis Factor-alpha / genetics*
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Amyloid
  • Antagomirs
  • Culture Media, Conditioned
  • Interleukin-8
  • MIRN142 microRNA, human
  • MicroRNAs
  • Tumor Necrosis Factor-alpha
  • Protein Kinase C-alpha
  • Tetradecanoylphorbol Acetate