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Updated: Feb 14, 2026

On-Chip Endothelial Inflammatory Phenotyping
Published on: July 21, 2012
MicroRNA-146 regulates the inflammatory cytokines expression in vascular endothelial cells during sepsis
Aims:
The purpose of this study was to investigate the functional role of microRNA (miR)-146 in sepsis, as well as the underlying mechanism.
Methods:
Human vascular endothelial cell line EA. hy926 cells were treated with lipopolysaccharide (LPS) and/or transfected with miR-146 mimics, inhibitor, and their corresponding controls. Expression of miR-146 was then analyzed after treatment and/or transfection, as well as the expression of inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, intercellular adhesion molecule (ICAM)-1, and E-selectin, and nuclear factor kappa B (NF-κB) binding activity.
Results:
The results showed that the expression of miR-146 was significantly downregulated by LPS stimulation compared to the control group (P < 0.05). Also, the expression of miR-146 was remarkably increased by miR-146 mimics but decreased by miR-146 inhibitor following stimulation with LPS (P < 0.05). In addition, the expression levels of TNF-α, IL-6, ICAM-1, and E-selectin were shown to increase following induction by LPS, and further markedly elevated by miR-146 inhibitor (all P < 0.05). However, the expression levels of these inflammatory cytokines were outstandingly decreased by miR-146 mimics (all P < 0.05). Moreover, we observed that the relative NF-κB activity was statistically upregulated by miR-146 inhibitor but downregulated by miR-146 mimics.
Conclusions:
MiR-146 may play an important role in the pathogenesis and development of sepsis by suppressing the expression of inflammatory cytokines.
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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