Chondroitin sulfate inhibits the nuclear translocation of nuclear factor-kappaB in interleukin-1beta-stimulated chondrocytes

Basic Clin Pharmacol Toxicol. 2008 Jan;102(1):59-65. doi: 10.1111/j.1742-7843.2007.00158.x. Epub 2007 Nov 5.

Abstract

Chondroitin sulfate is referred as a symptomatic slow-acting drug for osteoarthritis because it improves articular function, and reduces joint swelling and effusion. In addition, chondroitin sulfate prevents joint space narrowing of the knee. We hypothesized that the anti-inflammatory effect of chondroitin sulfate is associated to a decrease in the activation of mitogen-activated protein kinases (MAPK) and of the transcription factors nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1). Cultured rabbit chondrocytes were stimulated with interleukin-1beta (IL-1beta) in presence of chondroitin sulfate. Nuclear translocation of NF-kappaB and AP-1, and nitrite concentrations (as an index for nitric oxide) was assessed 48 hr later. The effect of chondroitin sulfate on IL-1beta activation of extracellular signal-regulated kinase 1/2 (Erk1/2) and p38MAPK was documented by immunoblot. The effect of chondroitin sulfate on sodium nitroprusside-induced apoptosis was evaluated with the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling assay. Chondroitin sulfate reduced IL-1beta-induced NF-kappaB nuclear translocation, but not AP-1 translocation, it decreased IL-1beta-induced phosphorylation of Erk1/2 and abrogated p38MAPK phosphorylation, but did not prevent IL-1beta-induced increase in nitrite. Finally, chondroitin sulfate decreased nitroprusside-induced apoptosis of the chondrocytes. These results suggest that some of the biological activities of chondroitin sulfate may be associated to the reduction in Erk1/2 and p38MAPK phosphorylation and nuclear transactivation of NF-kappaB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Bromodeoxyuridine / metabolism
  • Cartilage, Articular / cytology
  • Cell Nucleus / drug effects*
  • Cell Nucleus / metabolism
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Chondrocytes / drug effects*
  • Chondrocytes / metabolism
  • Chondrocytes / pathology
  • Chondroitin Sulfates / pharmacology*
  • Drug Antagonism
  • Drug Therapy, Combination
  • Flavonoids / pharmacology
  • Interleukin-1beta / pharmacology*
  • Male
  • Microscopy, Fluorescence
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • NF-kappa B / metabolism*
  • Nitrites / metabolism
  • Nitroprusside / pharmacology
  • Phosphorylation / drug effects
  • Protein Transport / drug effects
  • Rabbits
  • Transcription Factor AP-1 / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Flavonoids
  • Interleukin-1beta
  • NF-kappa B
  • Nitrites
  • Transcription Factor AP-1
  • Nitroprusside
  • Chondroitin Sulfates
  • Mitogen-Activated Protein Kinase 1
  • p38 Mitogen-Activated Protein Kinases
  • Bromodeoxyuridine
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one