Involvement of miR-Let7A in inflammatory response and cell survival/apoptosis regulated by resveratrol in THP-1 macrophage.
10.4162/nrp.2016.10.4.377
- Author:
Juhyun SONG
1
;
Mira JUN
;
Mok Ryeon AHN
;
Oh Yoen KIM
Author Information
1. Department of Biomedical Engineering, Dongguk University, Gyeonggi 10326, Korea.
- Publication Type:Original Article
- Keywords:
Resveratrol;
microRNA-Let7A;
inflammation;
ASK1;
sirtuin 1
- MeSH:
Apoptosis;
Brain-Derived Neurotrophic Factor;
Caspase 3;
Cell Survival;
Cytokines;
Humans;
Inflammation;
Interleukin-10;
Interleukin-4;
Interleukins;
Macrophages*;
MAP Kinase Kinase Kinase 5;
MicroRNAs;
Necrosis;
Oxidative Stress;
RNA, Messenger;
Sirtuin 1
- From:Nutrition Research and Practice
2016;10(4):377-384
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND/OBJECTIVES: Resveratrol, a natural polyphenol, has multiple functions in cellular responses including apoptosis, survival, and differentiation. It also participates in the regulation of inflammatory response and oxidative stress. MicroRNA-Let-7A (miR-Let7A), known as a tumor suppressor miRNA, was recently reported to play a crucial role in both inflammation and apoptosis. Therefore, we examined involvement of miR-Let7A in the modulation of inflammation and cell survival/apoptosis regulated by resveratrol. MATERIALS/METHODS: mRNA expression of pro-/anti-inflammatory cytokines and sirtuin 1 (SIRT1), and protein expression of apoptosis signal-regulating kinase 1 (ASK1), p-ASK1, and caspase-3 and cleaved caspase-3 were measured, and cell viability and Hoechst/PI staining for apoptosis were observed in Lipopolysaccharide (LPS)-stimulated human THP-1 macrophages with the treatment of resveratrol and/or miR-Let7A overexpression. RESULTS: Pre-treatment with resveratrol (25-200 µM) resulted in significant recovery of the reduced cell viabilities under LPS-induced inflammatory condition and in markedly increased expression of miR-Let7A in non-stimulated or LPS-stimulated cells. Increased mRNA levels of tumor necrosis factor-α and interleukin (IL)-6 induced by LPS were significantly attenuated, and decreased levels of IL-10 and brain-derived neurotrophic factor were significantly restored by resveratrol and miR-Let7A overexpression, respectively, or in combination. Decreased expression of IL-4 mRNA by LPS stimulation was also significantly increased by miR-Let7A overexpression co-treated with resveratrol. In addition, decreased SIRT1 mRNA levels, and increased p-ASK1 levels and PI-positive cells by LPS stimulation were significantly restored by resveratrol and miR-Let7A overexpression, respectively, or in combination. CONCLUSIONS: miR-Let7A may be involved in the inflammatory response and cell survival/apoptosis modulated by resveratrol in human THP-1 macrophages.
