Maresin 1 attenuates pro-inflammatory reactions and ER stress in HUVECs via PPARα-mediated pathway

Autor: Tae Woo Jung, Geum Hee Choi, Dong-Seok Kim, Sung Ho Ahn, Daehwan Kim, Hyung Sub Park, Taeseung Lee, Ji Hoon Jeong
Rok vydání: 2018
Předmět:
Zdroj: Molecular and Cellular Biochemistry. 448:335-347
ISSN: 1573-4919
0300-8177
Popis: The current study was designed to investigate the therapeutic effects of Maresin 1 (MAR1) on atherosclerotic response. Human monocytes THP-1 and human umbilical vein endothelial cells (HUVECs) were used to investigate the effects of MAR1 on lipopolysaccharide (LPS)-induced inflammation and apoptosis. In this study, we found that MAR1 induces peroxisome proliferator-activated receptor alpha (PPARα) expression. We also demonstrated that MAR1 suppresses atherosclerotic reactions caused by LPS treatment via a PPARα-dependent pathway. MAR1 treatment inhibited LPS-induced phosphorylation of nuclear factor kappa B (NF-κB) and secretion of pro-inflammatory cytokines in HUVECs and THP-1 cells. In HUVEC cells, expression of adhesion molecules and LPS-stimulated adhesion of THP-1 cells to the endothelium were significantly decreased after MAR1 treatment. Furthermore, LPS-induced endoplasmic reticulum (ER) stress and cell apoptosis was significantly decreased after MAR1 treatment of HUVECs. MAR1 also led to a dose-dependent increase in oxygen-regulated protein 150 (ORP150) expression which is responsible for the inhibition of ER stress. Notably, all of the pro-atherosclerotic effects were completely abrogated by treatment with small interfering (si) RNA targeting PPARα. In conclusion, MAR1 ameliorates LPS-induced atherosclerotic reactions via PPARα-mediated suppression of inflammation and ER stress.
Databáze: OpenAIRE
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