Previous studies have reported that low molecular mass HA and highly polymerized HA respectively elicited 25 pro- and anti-inflammatory responses by modulating the toll-like receptor 4 (TLR-4) and the TLR-2. The 26 activation of TLR-4 and TLR-2 mediated by collagen-induced arthritis (CIA) induces the myeloid 27 differentiation primary response protein (MyD88) and the tumor necrosis factor receptor-associated factor 28 6 (TRAF6), and ends with the liberation of NF-kB which, in turn, stimulates pro-inflammatory cytokine 29 production. The aim of this study was to investigate the influence of high molecular weight HA at different 30 concentrations on TLR-4 and TLR-2 modulation in CIA in mice. Arthritis was induced in mice via intradermal 31 injection of an emulsion containing bovine type II collagen in complete Freund's adjuvant. Mice were treated 32 with HA intraperitoneally daily for 30 days. CIA increased TLR-4, TLR-2, MyD88 and TRAF6 mRNA expression 33 and the related protein in the cartilage of arthritic joints. High levels of both mRNA and related protein were 34 also detected for tumor necrosis factor alpha (TNF-α), interleukin 1-beta (IL-1-β), interleukin-17 (IL-17), 35 matrixmetalloprotease-13 (MMP-13) and inducible nitric oxide synthase (iNOS) in the joint of arthriticmice. 36 HA treatment significantly limited CIA incidence and decreased all the parameters up-regulated by CIA. The 37 improvement of biochemical parameters was also supported by histological analysis, plasma and synovial 38 fluid HA levels. These results suggest that the TLR-4 and TLR-2 play an important role in the arthritis 39 mechanism and the interaction/block of HA at high molecular mass may reduce inflammation and cartilage 40 injury. 41
Hyaluronan reduces inflammation in experimental arthritis by modulating TLR-2 and TLR-4 cartilage expression
CAMPO, Giuseppe Maurizio;AVENOSO, Angela;NASTASI, GIANCARLO;MICALI, Antonio Girolamo;VACCARO, Mario;D'ASCOLA, ANGELA;CALATRONI, Alberto;CAMPO, Salvatore Giuseppe
2011-01-01
Abstract
Previous studies have reported that low molecular mass HA and highly polymerized HA respectively elicited 25 pro- and anti-inflammatory responses by modulating the toll-like receptor 4 (TLR-4) and the TLR-2. The 26 activation of TLR-4 and TLR-2 mediated by collagen-induced arthritis (CIA) induces the myeloid 27 differentiation primary response protein (MyD88) and the tumor necrosis factor receptor-associated factor 28 6 (TRAF6), and ends with the liberation of NF-kB which, in turn, stimulates pro-inflammatory cytokine 29 production. The aim of this study was to investigate the influence of high molecular weight HA at different 30 concentrations on TLR-4 and TLR-2 modulation in CIA in mice. Arthritis was induced in mice via intradermal 31 injection of an emulsion containing bovine type II collagen in complete Freund's adjuvant. Mice were treated 32 with HA intraperitoneally daily for 30 days. CIA increased TLR-4, TLR-2, MyD88 and TRAF6 mRNA expression 33 and the related protein in the cartilage of arthritic joints. High levels of both mRNA and related protein were 34 also detected for tumor necrosis factor alpha (TNF-α), interleukin 1-beta (IL-1-β), interleukin-17 (IL-17), 35 matrixmetalloprotease-13 (MMP-13) and inducible nitric oxide synthase (iNOS) in the joint of arthriticmice. 36 HA treatment significantly limited CIA incidence and decreased all the parameters up-regulated by CIA. The 37 improvement of biochemical parameters was also supported by histological analysis, plasma and synovial 38 fluid HA levels. These results suggest that the TLR-4 and TLR-2 play an important role in the arthritis 39 mechanism and the interaction/block of HA at high molecular mass may reduce inflammation and cartilage 40 injury. 41Pubblicazioni consigliate
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