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

Molecular and Cellular Biochemistry volume 448, pages 335–347 (2018)Cite this article

Abstract

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.

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Abbreviations

IL-6:

Interleukin 6

PPARα:

Peroxisome proliferator-activated receptor alpha

ORP150:

Oxygen-regulated protein 150

ER:

Endoplasmic reticulum

HFD:

High fat diet

UPR:

Unfolded protein response

CHOP:

C/EBP homologous protein

DHA:

Docosahexaenoic acid

MAR1:

Maresin 1

siRNA:

Small interfering RNA

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Funding

Contract grant sponsor: This study was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) grant funded by the Korea government Ministry of Education (2017R1D1A1B03028892) and the Ministry of Science, ICT, and Future Planning (2016R1C1B2012674).

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Affiliations

  1. Research Administration Team, Seoul National University Bundang Hospital, Seongnam, Republic of Korea

    Tae Woo Jung

  2. Department of Surgery, Seoul National University Bundang Hospital, 166 Gumi-ro, Bundang-gu, Seongnam, 463-707, Republic of Korea

    Tae Woo Jung, Hyung Sub Park, Geum Hee Choi, Daehwan Kim & Taeseung Lee

  3. Department of Pathology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea

    Sung Ho Ahn

  4. Department of Biochemistry, College of Medicine, Chung-Ang University, Seoul, Republic of Korea

    Dong-Seok Kim

  5. Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea

    Taeseung Lee

  6. Department of Pharmacology, College of Medicine, Chung-Ang University, 221, Heuksuk-dong, Dongjak-gu, Seoul, 156-756, Republic of Korea

    Ji Hoon Jeong

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  1. Tae Woo Jung
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  2. Hyung Sub Park
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  3. Geum Hee Choi
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Contributions

TWJ, TSL, and JHJ: substantial contribution to the conception and design; TWJ, HSP, and GHC: acquisition of data, or analysis and interpretation of data; TWJ, DHK, and DSK: drafting or revising the article. All authors approved the final version of the manuscript. TWJ, TSL, and JHJ are responsible for the integrity of the work as a whole.

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Correspondence to Taeseung Lee or Ji Hoon Jeong.

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Electronic supplementary material

MAR1 does not affect LPS-induced hydrogen peroxide production in HUVECs. Cells were treated with various concentrations of MAR1 (0, 5, or 10 μM) or LPS (200 ng/ml). After 24 h, the levels of hydrogen peroxide production were determined by colorimetric enzyme assay in HUVECs. Student’s t test was used for statistical analysis. Below is the link to the electronic supplementary material.

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Jung, T.W., Park, H.S., Choi, G.H. et al. Maresin 1 attenuates pro-inflammatory reactions and ER stress in HUVECs via PPARα-mediated pathway. Mol Cell Biochem 448, 335–347 (2018). https://doi.org/10.1007/s11010-018-3392-y

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Keywords

  • Maresin 1
  • Peroxisome proliferator-activated receptor alpha
  • Oxygen-regulated protein 150
  • Inflammation
  • Apoptosis
  • Atherosclerosis