Hyaluronan reduces inflammation in experimental arthritis by modulating TLR-2 and TLR-4 cartilage expression

被引：118
作者：
Campo, Giuseppe M. [1 ]
Avenoso, Angela [1 ]
Nastasi, Giancarlo [1 ]
Micali, Antonio [2 ]
Prestipino, Vera [1 ]
Vaccaro, Mario [3 ]
D'Ascola, Angela [1 ]
Calatroni, Alberto [1 ]
Campo, Salvatore [1 ]
机构：
[1] Univ Messina, Sch Med, Dept Biochem Physiol & Nutr Sci, Policlin Univ,Sect Med Chem, I-98125 Messina, Italy
[2] Univ Messina, Sch Med, Dept Biomorphol & Biotechnol, Policlin Univ, I-98125 Messina, Italy
[3] Univ Messina, Sch Med, Inst Dermatol, Policlin Univ, I-98125 Messina, Italy
来源：
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE | 2011年 / 1812卷 / 09期
关键词：
NF-kB; Toll-like receptor; Cytokine; TNF-alpha; Arthritis; Hyaluronan; TOLL-LIKE RECEPTORS; COLLAGEN-INDUCED ARTHRITIS; ANTIGEN-INDUCED ARTHRITIS; SYNOVIAL TISSUE; DANGER SIGNAL; FRAGMENTS; TOLL-LIKE-RECEPTOR-4; GLYCOSAMINOGLYCANS; ACID; REACTIVATION;
D O I：
10.1016/j.bbadis.2011.06.006
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Previous studies have reported that low molecular mass HA and highly polymerized HA respectively elicited pro- and anti-inflammatory responses by modulating the toll-like receptor 4 (TLR-4) and the TLR-2. The activation of TLR-4 and TLR-2 mediated by collagen-induced arthritis (CIA) induces the myeloid differentiation primary response protein (MyD88) and the tumor necrosis factor receptor-associated factor 6 (TRAF6), and ends with the liberation of NF-kB which, in turn, stimulates pro-inflammatory cytokine production. The aim of this study was to investigate the influence of high molecular weight HA at different concentrations on TLR-4 and TLR-2 modulation in CIA in mice. Arthritis was induced in mice via intradermal injection of an emulsion containing bovine type II collagen in complete Freund's adjuvant. Mice were treated with HA intraperitoneally daily for 30 days. CIA increased TLR-4, TLR-2, MyD88 and TRAF6 mRNA expression and the related protein in the cartilage of arthritic joints. High levels of both mRNA and related protein were also detected for tumor necrosis factor alpha (INF-alpha), interleukin 1-beta (IL-1-beta), interleukin-17 (IL-17), matrix metalloprotease-13 (MMP-13) and inducible nitric oxide synthase (iNOS) in the joint of arthritic mice. HA treatment significantly limited CIA incidence and decreased all the parameters up-regulated by CIA. The improvement of biochemical parameters was also supported by histological analysis, plasma and synovial fluid HA levels. These results suggest that the TLR-4 and TLR-2 play an important role in the arthritis mechanism and the interaction/block of HA at high molecular mass may reduce inflammation and cartilage injury. (C) 2011 Elsevier B.V. All rights reserved.
引用
收藏
页码：1170 / 1181
页数：12
相关论文
共 53 条
[11]   Systemic administration of high-molecular weight hyaluronan stimulates wound healing in genetically diabetic mice [J].
Galeano, Mariarosaria ;
Polito, Francesca ;
Bitto, Alessandra ;
Irrera, Natasha ;
Campo, Giuseppe M. ;
Avenoso, Angela ;
Calo, Margherita ;
Lo Cascio, Patrizia ;
Minutoli, Letteria ;
Barone, Mauro ;
Squadrito, Francesco ;
Altavilla, Domenica .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 2011, 1812 (07) :752-759
[12]   Low molecular weight hyaluronic acid increases the self-defense of skin epithelium by induction of β-defensin 2 via TLR2 and TLR4 [J].
Gariboldi, Silvia ;
Palazzo, Marco ;
Zanobbio, Laura ;
Selleri, Silvia ;
Sommariva, Michele ;
Sfondrini, Lucia ;
Cavicchini, Stefano ;
Balsari, Andrea ;
Rumio, Cristiano .
JOURNAL OF IMMUNOLOGY, 2008, 181 (03) :2103-2110
[13]   New regulators of NF-κB in inflammation [J].
Ghosh, Sankar ;
Hayden, Matthew S. .
NATURE REVIEWS IMMUNOLOGY, 2008, 8 (11) :837-848
[14]   The role of intra-articular hyaluronan (SinovialA®) in the treatment of osteoarthritis [J].
Gigante, Antonio ;
Callegari, Leonardo .
RHEUMATOLOGY INTERNATIONAL, 2011, 31 (04) :427-444
[15]   Cartilage homeostasis in health and rheumatic diseases [J].
Goldring, Mary B. ;
Marcu, Kenneth B. .
ARTHRITIS RESEARCH & THERAPY, 2009, 11 (03)
[16]   High molecular weight hyaluronic acid inhibits IL-6-induced MMP production from human chondrocytes by up-regulating the ERK inhibitor, MKP-1 [J].
Hashizume, Misato ;
Mihara, Masahiko .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2010, 403 (02) :184-189
[17]   Increased macrophage activation mediated through toll-like receptors in rheumatoid arthritis [J].
Huang, QiQuan ;
Ma, Yingyu ;
Adebayo, Adedamola ;
Pope, Richard M. .
ARTHRITIS AND RHEUMATISM, 2007, 56 (07) :2192-2201
[18]   Regulation of lung injury and repair by Toll-like receptors and hyaluronan [J].
Jiang, DH ;
Liang, JR ;
Fan, J ;
Yu, S ;
Chen, SP ;
Luo, Y ;
Prestwich, GD ;
Mascarenhas, MM ;
Garg, HG ;
Quinn, DA ;
Homer, RJ ;
Goldstein, DR ;
Bucala, R ;
Lee, PJ ;
Medzhitov, R ;
Noble, PW .
NATURE MEDICINE, 2005, 11 (11) :1173-1179
[19]   Hyaluronan in tissue injury and repair [J].
Jiang, Dianhua ;
Liang, Jiurong ;
Noble, Paul W. .
ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, 2007, 23 :435-461
[20]   Receptor-mediated monitoring of tissue well-being via detection of soluble heparan sulfate by toll-like receptor 4 [J].
Johnson, GB ;
Brunn, GJ ;
Kodaira, Y ;
Platt, JL .
JOURNAL OF IMMUNOLOGY, 2002, 168 (10) :5233-5239
123456