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Resveratrol Exerts Anti-Osteoarthritic Effect by Inhibiting TLR4/NF-κB Signaling Pathway via the TLR4/Akt/FoxO1 Axis

Xiaolei Xu1,2, Xudan Liu1, Yingchun Yang1

  • 1Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, Shenyang, People's Republic of China.

Drug Design, Development and Therapy
|June 26, 2020
PubMed
Abstract

Insights

Resveratrol enhances the anti-inflammatory TLR4/Akt/FoxO1 pathway, reducing inflammation in osteoarthritis (OA). This study reveals how resveratrol boosts this self-limiting mechanism, offering potential for OA treatment.

Area of Science:

  • Cell biology
  • Molecular biology
  • Immunology

Background:

  • Osteoarthritis (OA) is characterized by chronic low-grade inflammation.
  • Resveratrol exhibits anti-inflammatory properties with potential benefits for OA.
  • The precise mechanisms of resveratrol's anti-inflammatory effects on signaling pathways require further elucidation.

Purpose of the Study:

  • To investigate the link between resveratrol-mediated PI3K/Akt expression and the TLR4/NF-κB pathway.
  • To explore the role of the TLR4/Akt/FoxO1 axis in resveratrol's anti-osteoarthritic effects.

Main Methods:

  • SW1353 cells were stimulated with IL-1β and treated with resveratrol, TLR4 siRNA, PI3K inhibitor LY294002, or FoxO1 siRNA.
  • Western blot analysis was used to assess protein expression related to TLR4 signaling and the TLR4/Akt/FoxO1 axis.
  • Enzyme-linked immunosorbent assay (ELISA) measured IL-6 levels in the cell supernatant.

Main Results:

  • IL-1β increased TLR4/NF-κB expression and PI3K/Akt/FoxO1 phosphorylation; resveratrol further upregulated PI3K/Akt/FoxO1 phosphorylation while downregulating TLR4.
  • Inhibition studies revealed that TLR4 activation induces PI3K/Akt phosphorylation, leading to FoxO1 phosphorylation and inactivation.
  • Inactivated FoxO1 reduces TLR4 expression, establishing a self-limiting inflammatory mechanism that resveratrol enhances.

Conclusions:

  • A TLR4/Akt/FoxO1 inflammatory self-limiting mechanism exists in IL-1β-stimulated SW1353 cells.
  • A novel cross-talk between the PI3K/Akt/FoxO1 network and TLR4-driven innate responses was identified.
  • Resveratrol may exert anti-osteoarthritic effects by bolstering this inflammatory self-limiting mechanism via the TLR4/Akt/FoxO1 axis.
Keywords:
forkhead box O1interleukin-1βosteoarthritisphosphoinositide-3-kinase/protein kinase Bresveratroltoll-like receptor 4

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