MicroRNA-146 regulates the inflammatory cytokines expression in vascular endothelial cells during sepsis

Die Pharmazie
|February 15, 2018
PubMed
Abstract

Insights

MicroRNA-146 (miR-146) is downregulated in sepsis and suppresses inflammatory cytokines. Restoring miR-146 levels reduces sepsis-related inflammation and nuclear factor kappa B (NF-κB) activity.

Area of Science:

  • Molecular Biology
  • Immunology
  • Sepsis Pathogenesis

Background:

  • Sepsis is a life-threatening condition characterized by dysregulated host response to infection.
  • MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and play roles in various biological processes, including inflammation.
  • The specific role of miR-146 in sepsis pathogenesis requires further elucidation.

Purpose of the Study:

  • To investigate the functional role of microRNA-146 (miR-146) in sepsis.
  • To elucidate the underlying molecular mechanisms by which miR-146 influences sepsis development.

Main Methods:

  • Human vascular endothelial cells (EA.hy926) were stimulated with lipopolysaccharide (LPS) and transfected with miR-146 mimics or inhibitors.
  • Expression levels of miR-146, inflammatory cytokines (TNF-α, IL-6, ICAM-1, E-selectin), and NF-κB activity were analyzed.

Main Results:

  • LPS stimulation significantly downregulated miR-146 expression.
  • miR-146 mimics increased miR-146 expression, while inhibitors decreased it, in LPS-treated cells.
  • miR-146 mimics suppressed the LPS-induced upregulation of inflammatory cytokines and NF-κB activity, whereas miR-146 inhibitors exacerbated these effects.

Conclusions:

  • MiR-146 plays a crucial role in sepsis pathogenesis.
  • MiR-146 suppresses the expression of inflammatory cytokines, potentially by inhibiting NF-κB signaling.
  • Modulating miR-146 levels may represent a therapeutic strategy for sepsis.

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