Resveratrol regulates the inflammation and oxidative stress of granulosa cells in PCOS via targeting TLR2

J Bioenerg Biomembr. 2022 Aug;54(4):191-201. doi: 10.1007/s10863-022-09942-7. Epub 2022 Jul 14.

Abstract

Polycystic ovary syndrome (PCOS) is featured as a common endocrine disorder in reproductive-aged women, while its pathophysiology is not fully illustrated. This study examined potential actions of resveratrol in PCOS cellular model and explored the underlying interaction between resveratrol and toll-like receptor 2 (TLR2). This study performed the bioinformatics analysis on two microarray datasets (GSE34526 and GSE138518). We found that TLR2 was one of potential hub genes that may be associated with PCOS. Further examination showed that TLR2 was highly expressed in granulosa cells from PCOS group compared with control. The in vitro studies showed that LPS intervention caused an increased expression of TLR2 and the pro-inflammatory mediators, and induced oxidative stress in the granulosa cells, which was concentration-dependently antagonized by resveratrol treatment. TLR2 silence significantly attenuated LPS-induced increase TNF-α, IL-1β, IL-6 and IL-8 expression and oxidative stress of granulosa cells. Furthermore, TLR2 overexpression promoted inflammatory response and oxidative stress in the granulosa cells, which was antagonized by resveratrol treatment. In conclusion, resveratrol could attenuate LPS-induced inflammation and oxidative stress in granulosa cells, and the underlying mechanisms may be related to the inhibitory effect of resveratrol on TLR2 expression in granulosa cells.

Keywords: Granulosa cells; Inflammation; Oxidative stress; PCOS; Resveratrol; TLR2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Granulosa Cells
  • Humans
  • Inflammation / genetics
  • Interleukin-6 / metabolism
  • Interleukin-6 / pharmacology
  • Interleukin-8 / metabolism
  • Interleukin-8 / pharmacology
  • Lipopolysaccharides / pharmacology
  • Oxidative Stress
  • Polycystic Ovary Syndrome* / drug therapy
  • Polycystic Ovary Syndrome* / genetics
  • Polycystic Ovary Syndrome* / metabolism
  • Resveratrol / metabolism
  • Resveratrol / pharmacology
  • Resveratrol / therapeutic use
  • Toll-Like Receptor 2 / metabolism
  • Tumor Necrosis Factor-alpha

Substances

  • Interleukin-6
  • Interleukin-8
  • Lipopolysaccharides
  • TLR2 protein, human
  • Toll-Like Receptor 2
  • Tumor Necrosis Factor-alpha
  • Resveratrol