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Salsalate ameliorates the atherosclerotic response through HO-1- and SIRT1-mediated suppression of ER stress and inflammation
- Source :
- Inflammation Research. 68:655-663
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
Abstract
- Inflammation plays a causative role in atherosclerosis development. Salsalate is an anti-inflammatory drug used to treat atherosclerosis, but the mechanisms by which it affects atherosclerotic progression remain unclear. Human umbilical vascular endothelial cells (HUVECs) and THP-1 human monocytes were treated with salsalate. Heme oxygenase 1 (HO-1) and sirtuin 1 (SIRT1) small interfering RNAs (siRNAs) were used to suppress each gene expression. Protein analyses were performed for measuring the expression of HO-1, SIRT1, nuclear factor kappa B (NFκB), cell adhesion molecules, and endoplasmic reticulum (ER) stress markers. Furthermore, cell adhesion assay, caspase 3 activity assay, and ELISA were also performed. In this study, we show that salsalate increases the expression of HO-1 and SIRT1 in HUVEC and suppresses lipopolysaccharide (LPS)-induced atherosclerotic responses via HO-1- and SIRT1-mediated pathways. Salsalate treatment of HUVEC and THP-1 cells reduced LPS-induced phosphorylation of NFκB and secretion of the proinflammatory cytokines TNFα and MCP-1. Salsalate treatment of HUVEC reduced the expression of the adhesion molecules ICAM, VCAM, and E-selectin and the LPS-induced adhesion of THP-1 cells to HUVEC. Salsalate treatment also attenuated LPS-induced ER stress and cell apoptosis. These anti-atherosclerotic effects were reversed by treating cells with siRNA for HO-1 and SIRT1. Salsalate ameliorates LPS-induced atherosclerotic reactions via HO-1 and SIRT1-dependent reduction of inflammation and ER stress. Activation of these pathways by salsalate may provide therapeutic strategies for treating atherosclerosis.
- Subjects :
- Lipopolysaccharides
0301 basic medicine
THP-1 Cells
Immunology
Inflammation
Proinflammatory cytokine
03 medical and health sciences
0302 clinical medicine
Sirtuin 1
Human Umbilical Vein Endothelial Cells
medicine
Salsalate
Humans
RNA, Small Interfering
Cell adhesion
Chemokine CCL2
Pharmacology
Tumor Necrosis Factor-alpha
Chemistry
Cell adhesion molecule
NF-kappa B
Atherosclerosis
Endoplasmic Reticulum Stress
Salicylates
Heme oxygenase
030104 developmental biology
030220 oncology & carcinogenesis
Unfolded protein response
Cancer research
lipids (amino acids, peptides, and proteins)
Tumor necrosis factor alpha
medicine.symptom
Heme Oxygenase-1
medicine.drug
Subjects
Details
- ISSN :
- 1420908X and 10233830
- Volume :
- 68
- Database :
- OpenAIRE
- Journal :
- Inflammation Research
- Accession number :
- edsair.doi.dedup.....98b064b3dcb6eb908f4d94ac62ff91c6