Inhibition of nuclear factor-kappaB by hyaluronan in rheumatoid chondrocytes stimulated with COOH-terminal heparin-binding fibronectin fragment.

Abstract

The aim of this study was to examine the inhibitory effect of high molecular weight hyaluronan (HA) on nuclear factor (NF)-kappaB activation by COOH-terminal heparin-binding fibronectin fragment (HBFN-f) in rheumatoid arthritis (RA) chondrocytes. When RA chondrocytes in monolayer or cartilage explants were cultured with HBFN-f, the fragment stimulated the phosphorylation and nuclear translocation of NF-kappaB, leading to nitric oxide (NO) production in association with inducible form of NO synthase (iNOS) up-regulation. Inhibition studies with NF-kappaB inhibitors indicated the requirement of NF-kappaB for HBFN-f-induced NO production. Pretreatment with 2700 kDa HA resulted in significant suppression of NF-kappaB activation by HBFN-f. HA also inhibited HBFN-f-stimulated NO production with down-regulation of iNOS. The present study clearly demonstrated that high molecular weight HA suppressed HBFN-f-activated NF-kappaB in RA chondrocytes. HA could down-regulate the catabolic action of fibronectin fragments like HBFN-f in RA joints as a potent NF-kappaB inhibitor.

• Authors: Tadashi Yasuda, Takashi Nakamura
• Journal: Modern rheumatology (Mod Rheumatol) Vol. 17 Issue 5 Pg. 391-7 ( 2007) ISSN: 1439-7595 [Print] England
• PMID: 17929131 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Fibronectins
• NF-kappa B
• Nitric Oxide
• Hyaluronic Acid
• Heparin
• Chymotrypsin
• alpha-chymotrypsin

Topics

• Arthritis, Rheumatoid (drug therapy, metabolism)
• Cartilage (metabolism)
• Cartilage, Articular (metabolism)
• Cell Nucleus (metabolism)
• Chondrocytes (metabolism)
• Chymotrypsin (pharmacology)
• Fibronectins (chemistry, metabolism)
• Gene Expression Regulation
• Heparin (chemistry)
• Humans
• Hyaluronic Acid (metabolism, pharmacology)
• Models, Biological
• NF-kappa B (metabolism)
• Nitric Oxide (metabolism)
• Protein Binding
• Protein Structure, Tertiary