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


Jung T. W., Pyun D. H., Kim T. J., Lee H. J., Park E. S., Abd El-Aty A. M., ...Daha Fazla

Advances in Medical Sciences, cilt.66, sa.1, ss.155-161, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 66 Sayı: 1
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1016/j.advms.2021.01.007
  • Dergi Adı: Advances in Medical Sciences
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, EMBASE, Food Science & Technology Abstracts, MEDLINE
  • Sayfa Sayıları: ss.155-161
  • Anahtar Kelimeler: METRNL, HUVEC, THP-1, Inflammation, AMPK, PPAR delta, PROLIFERATOR-ACTIVATED-RECEPTOR, INSULIN-RESISTANCE, NUCLEAR RECEPTORS, ATHEROSCLEROSIS, METABOLISM, EXPRESSION, ADIPOSE, MUSCLE
  • Atatürk Üniversitesi Adresli: Evet

Özet

© 2021 Medical University of BialystokPurpose: 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.