Meteorin-like protein (METRNL)/IL-41 improves LPS-induced inflammatory responses via AMPK or PPARδ-mediated signaling pathways

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 NF kappa B and I kappa B 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 TNF alpha and MCP-1 in culture medium. Results: Treatment with METRNL suppressed the secretion of TNF alpha and MCP-1 as well as NF kappa B and I kappa B 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 PPAR delta expression in a dose-dependent manner. Small interference (si) RNA-mediated suppression of AMPK or PPAR delta restored all these changes. Conclusions: It has therefore been shown that METRNL ameliorates inflammatory responses through AMPK and PPAR delta-dependent pathways in LPS-treated HUVEC. In sum, the current study may suggest the suppressive potential of METRNL against endothelial inflammation.