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.

Abstract

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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