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Updated: Nov 17, 2025

Screening Assays to Characterize Novel Endothelial Regulators Involved in the Inflammatory Response
Published on: September 15, 2017
Meteorin-like protein (METRNL)/IL-41 improves LPS-induced inflammatory responses via AMPK or PPARδ-mediated signaling
Tae Woo Jung1, Do Hyeon Pyun1, Tae Jin Kim1
1Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea.
Purpose:
Meteorin-like protein (METRNL) (also known as IL-41), recently identified as a myokine, is released in response to muscle contraction. It improves the skeletal muscle insulin sensitivity through exerting a beneficial anti-inflammatory effect. However, no independent studies have been published to verify the effects of METRNL on human umbilical vein endothelial cells (HUVECs) and THP-1 human monocytes.
Materials And Methods:
The levels of NFκB and IκB phosphorylation as well as the expression of adhesion molecules were assessed by Western blotting analysis. Cell adhesion assay demonstrated the interactions between HUVEC and THP-1 cells. We used enzyme-linked immunosorbent assay (ELISA) to measure the levels of TNFα and MCP-1 in culture medium.
Results:
Treatment with METRNL suppressed the secretion of TNFα and MCP-1 as well as NFκB and IκB phosphorylation and inflammatory markers in lipopolysaccharide (LPS)-treated HUVECs and THP-1 cells. Furthermore, treatment with METRNL ameliorated LPS-induced attachment of THP-1 monocytes to HUVECs via inhibition of adhesion molecule expression and apoptosis. Treatment of HUVEC and THP-1 cells with METRNL enhanced AMPK phosphorylation and PPARδ expression in a dose-dependent manner. Small interference (si) RNA-mediated suppression of AMPK or PPARδ restored all these changes.
Conclusions:
It has therefore been shown that METRNL ameliorates inflammatory responses through AMPK and PPARδ-dependent pathways in LPS-treated HUVEC. In sum, the current study may suggest the suppressive potential of METRNL against endothelial inflammation.
Insights
Meteorin-like protein (METRNL) reduces inflammation in endothelial cells and monocytes. METRNL acts via AMPK and PPARδ pathways, suggesting its potential to suppress endothelial inflammation.
Area of Science:
- Endocrinology
- Immunology
- Cell Biology
Background:
- Meteorin-like protein (METRNL), a myokine, is released during muscle contraction.
- METRNL enhances skeletal muscle insulin sensitivity and possesses anti-inflammatory properties.
- The effects of METRNL on human umbilical vein endothelial cells (HUVECs) and THP-1 monocytes remain unverified.
Purpose of the Study:
- To investigate the anti-inflammatory effects of METRNL on HUVECs and THP-1 monocytes.
- To elucidate the molecular mechanisms underlying METRNL's action in endothelial inflammation.
Main Methods:
- Western blotting to assess NFκB and IκB phosphorylation and adhesion molecule expression.
- Cell adhesion assays to quantify THP-1 monocyte attachment to HUVECs.
- ELISA to measure TNFα and MCP-1 levels.
- siRNA to suppress AMPK and PPARδ.
Main Results:
- METRNL suppressed TNFα, MCP-1, NFκB/IκB phosphorylation, and inflammatory markers in LPS-treated HUVECs and THP-1 cells.
- METRNL reduced LPS-induced THP-1 monocyte adhesion to HUVECs by inhibiting adhesion molecules and apoptosis.
- METRNL dose-dependently enhanced AMPK and PPARδ phosphorylation/expression, which was reversed by siRNA suppression.
Conclusions:
- METRNL ameliorates inflammatory responses in LPS-treated HUVECs via AMPK and PPARδ-dependent pathways.
- METRNL demonstrates suppressive potential against endothelial inflammation.
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