Inhibition of nuclear factor-kappaB by hyaluronan in rheumatoid chondrocytes stimulated with COOH-terminal heparin-binding fibronectin fragment.
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.
Yasuda
Tadashi
T
Department of Sports Medicine, Faculty of Health, Budo, and Sports Studies, Tenri University, 80 Tainosho-cho, Tenri, 632-0071, Japan. tadyasu@sta.tenri-u.ac.jp
Nakamura
Takashi
T
D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism*; D002356:Cartilage / Q000378:metabolism; D002358:Cartilage, Articular / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D019902:Chondrocytes / Q000378:metabolism*; D002918:Chymotrypsin / Q000494:pharmacology; D005353:Fibronectins / Q000737:chemistry* / Q000378:metabolism; D005786:Gene Expression Regulation; D006493:Heparin / Q000737:chemistry*; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism / Q000494:pharmacology*; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary
D005353:Fibronectins; D016328:NF-kappa B; D009569:Nitric Oxide; D006820:Hyaluronic Acid; D006493:Heparin; D002918:Chymotrypsin; C117608:alpha-chymotrypsin