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Febuxostat mitigates IL-18-induced inflammatory response and reduction of extracellular matrix gene

Qin Geng1, Hongju Zhang1, Yanhui Cui1

  • 1Department of Rheumatology, Shandong Zibo Central Hospital Zibo 255036, Shandong, China.

American Journal of Translational Research
|April 12, 2021
PubMed
Abstract

Insights

Febuxostat protects chondrocytes from IL-18 damage by reducing inflammation and promoting extracellular matrix production, potentially through Sox-9 regulation. This offers a new therapeutic avenue for osteoarthritis.

Area of Science:

  • Cell Biology
  • Immunology
  • Rheumatology

Background:

  • Osteoarthritis (OA) pathogenesis involves extracellular matrix reduction and inflammation.
  • Elderly populations are primarily affected by osteoarthritis.
  • Interleukin-18 (IL-18) plays a role in OA-related chondrocyte damage.

Purpose of the Study:

  • To investigate Febuxostat's protective effects on chondrocytes against IL-18-induced damage.
  • To elucidate the underlying mechanism of Febuxostat's action in chondrocytes.

Main Methods:

  • Chondrocyte viability assessed via MTT assay.
  • Gene and protein expression analyzed using qRT-PCR and ELISA (IL-6, TNF-α, CCL5, iNOS, Col2a1, Acan, Sox-9).
  • Glycosaminoglycan (GAG) accumulation measured by Alcian blue assay; Nitric oxide (NO) production detected by DAF-FM DA staining.

Main Results:

  • Febuxostat counteracted IL-18-induced upregulation of IL-6, TNF-α, CCL5, iNOS, and NO.
  • IL-18 reduced Col2a1, Acan, and Sox-9 expression, while Febuxostat promoted them.
  • Sox-9 knockdown abolished Febuxostat's promotion of Col2a1 and Acan gene expression.

Conclusions:

  • Febuxostat mitigates IL-18-induced inflammation in chondrocytes.
  • Febuxostat's protective effects involve promoting extracellular matrix gene expression via Sox-9.
  • Febuxostat shows potential as a therapeutic agent for osteoarthritis.
Keywords:
IL-18OsteoarthritisSox-9chondrocytesextracellular matrix

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