Glycosaminoglycans reduced inflammatory response by modulating toll-like receptor-4 in LPS-stimulated chondrocytes

• Published in: Archives of biochemistry and biophysics Vol. 491; no. 1; pp. 7 - 15
• Main Authors: Campo, Giuseppe M., Avenoso, Angela, Campo, Salvatore, Traina, Paola, D’Ascola, Angela, Calatroni, Alberto
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-11-2009
• Subjects: Animals; Antibody Specificity; Blotting, Western; Cattle; Cells, Cultured; Chondrocytes; Chondrocytes - drug effects; Chondrocytes - metabolism; Cytokines; Gene Expression Regulation - drug effects; Glycosaminoglycans; Glycosaminoglycans - pharmacology; Inflammation; Inflammation - metabolism; Interleukin-1beta - genetics; Interleukin-1beta - metabolism; Lipopolysaccharide; Lipopolysaccharides - pharmacology; Matrix Metalloproteinase 13 - genetics; Matrix Metalloproteinase 13 - metabolism; Mice; Myeloid Differentiation Factor 88 - genetics; Myeloid Differentiation Factor 88 - metabolism; NF-kappa B - metabolism; Nitric Oxide Synthase Type II - genetics; Nitric Oxide Synthase Type II - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; TNF Receptor-Associated Factor 6 - genetics; TNF Receptor-Associated Factor 6 - metabolism; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - immunology; Toll-Like Receptor 4 - metabolism; Toll-like receptor-4; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism; Lipopolysaccharide; Toll-like receptor-4; Inflammation; Glycosaminoglycans; Cytokines; Chondrocytes
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2009.09.017

Lipopolysaccharide (LPS)-mediated activation of toll-like receptor-4 (TLR-4) complex induces specific signaling pathways, such as the myeloid differentiation primary response protein-88 (MyD88) and the tumor necrosis factor receptor-associated factor-6 (TRAF-6), involving NF-κB activation. As previous data reported that hyaluronan (HA) and heparan sulfate (HS) may interact with TLR-4, the aim of this study was to investigate whether glycosaminoglycans (GAGs) may modulate the TLR-4 receptor in a model of LPS-induced inflammatory cytokines in mouse chondrocytes. LPS stimulation up-regulated all inflammation parameters. The GAG treatment produced various effects: HA reduced MyD88 and TRAF-6 levels and NF-κB activation at the higher dose only, and exerted a very low anti-inflammatory effect; chondroitin-4-sulfate (C4S) and chondroitin-6-sulfate significantly inhibited MyD88, TRAF-6 and NF-κB activation, the inflammation cytokines, and inducible nitric oxide synthase; HS, like C4S, significantly reduced MyD88, TRAF-6, NF-κB and inflammation. Specific TLR-4 blocking antibody confirmed that TLR-4 was the target of GAG action.