title: Involvement of miR-Let7A in inflammatory response and cell survival/apoptosis regulated by resveratrol in THP-1 macrophage.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Biomedical Engineering, Dongguk University, Gyeonggi 10326, Korea.; Department of Biology, York University, Toronto, Ontario, Canada.
authors.forename: Juhyun
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Food Science and Nutrition, Dong-A University, 37 Nakdong-daero 550beon-gil, Saha-gu, Busan 49315, Korea.
authors.forename: Mira
authors.initials: M
authors.lastname: Jun
authors.affiliation: Department of Food Science and Nutrition, Dong-A University, 37 Nakdong-daero 550beon-gil, Saha-gu, Busan 49315, Korea.
authors.forename: Mok-Ryeon
authors.initials: MR
authors.lastname: Ahn
authors.affiliation: Department of Food Science and Nutrition, Dong-A University, 37 Nakdong-daero 550beon-gil, Saha-gu, Busan 49315, Korea.
authors.forename: Oh Yoen
authors.initials: OY
authors.lastname: Kim
keywords: ASK1; Resveratrol; inflammation; microRNA-Let7A; sirtuin 1