Involvement of miR-Let7A in inflammatory response and cell survival/apoptosis regulated by resveratrol in THP-1 macrophage

Juhyun Song; Mira Jun; Mok-Ryeon Ahn; Oh Yoen Kim

doi:10.4162/nrp.2016.10.4.377

Involvement of miR-Let7A in inflammatory response and cell survival/apoptosis regulated by resveratrol in THP-1 macrophage

Nutr Res Pract. 2016 Aug;10(4):377-84. doi: 10.4162/nrp.2016.10.4.377. Epub 2016 Jun 16.

Authors

Juhyun Song¹, Mira Jun², Mok-Ryeon Ahn², Oh Yoen Kim²

Affiliations

¹ Department of Biomedical Engineering, Dongguk University, Gyeonggi 10326, Korea.; Department of Biology, York University, Toronto, Ontario, Canada.
² Department of Food Science and Nutrition, Dong-A University, 37 Nakdong-daero 550beon-gil, Saha-gu, Busan 49315, Korea.

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.

Keywords: ASK1; Resveratrol; inflammation; microRNA-Let7A; sirtuin 1.