Chondroitin-4-sulphate inhibits NF-κB translocation and caspase activation in collagen-induced arthritis in mice

被引:45
作者
Campo, G. M. [1 ]
Avenoso, A. [1 ]
Campo, S. [1 ]
D'Ascola, A. [1 ]
Traina, P. [1 ]
Calatroni, A. [1 ]
机构
[1] Univ Messina, Sch Med, Policlin Univ, Dept Biochem Physiol & Nutr Sci,Sect Med Chem, I-98125 Messina, Italy
关键词
Chondroitin sulphate; NF-kappa B; Caspases; Arthritis; Antioxidants; Lipid peroxidation;
D O I
10.1016/j.joca.2008.04.002
中图分类号
R826.8 [整形外科学]; R782.2 [口腔颌面部整形外科学]; R726.2 [小儿整形外科学]; R62 [整形外科学(修复外科学)];
学科分类号
摘要
Objective: Free radical damage, inflammation, and apoptosis play a critical role in the onset and progression of cartilage erosion in arthritis. Many studies have demonstrated that glycosaminoglycans (GAGs), and chondroitin-4-sulphate (C4S) in particular, possess antioxidant activity that is able to inhibit lipid peroxidation which is the main mechanism of free radical-mediated biological injury. In addition to the effect directly exerted by reactive oxygen species (ROS), the activation of nuclear factor kappa B (NF-kappa B) and caspases may contribute substantially to increase inflammation and cell damage. We studied whether the antioxidant action of chronic C4S treatment to reduce ROS injury involves NF-kappa B and caspases modulation using an experimental model of collagen-induced arthritis in mice. Methods: Arthritis was induced in mice via an intradermal injection at the base of the tail of 100 mu l of emulsion containing bovine type II collagen in complete Freund's adjuvant. Results: Arthritis provoked the following: severe oedema and inflammation in the hind paws; lipid peroxidation in the joints [measured by 8-isoprostane (8-IPE) levels]; reduction of the endogenous antioxidants catalase (CAT) activity and reduced glutathione (GSH) levels; induction of NF-kappa B translocation; a loss of cytoplasmic NF-kappa B inhibitor alpha (IkB alpha.); an increase in metalloproteinase-13 (MMP-13), caspase-3 and caspase-7 gene expression and their related protein; the induction of cartilage polymorphonuclear (PMN) activation and infiltration [evaluated by elastase (ELA) assay] and cartilage alterations evaluated by histological analysis. Intraperitoneal administration of different doses of C4S (for 25 days), ameliorated all the symptoms of inflammation in the articular knee and paw joints, limited lipid peroxidation, inhibited NF-kappa B activation and IkB alpha. protein loss, decreased mRNA MMP-13 and caspases expression and their related protein, restored endogenous antioxidants, and reduced PMN accumulation in the damaged cartilage. Conclusion: The evidence that C4S was able to inhibit NF-kappa B and apoptosis activation supports the hypothesis that the C4S effect depends on reduction of ROS production, although other direct effects cannot be excluded. (C) 2008 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:1474 / 1483
页数:10
相关论文
共 36 条
[21]   NF-κB activation as a pathological mechanism of septic shock and inflammation [J].
Liu, SF ;
Malik, AB .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2006, 290 (04) :L622-L645
[22]   Grape seed proanthocyanidins inhibit UV-radiation-induced oxidative stress and activation of MAPK and NF-κB signaling in human epidermal keratinocytes [J].
Mantena, Sudheer K. ;
Katiyar, Santosh K. .
FREE RADICAL BIOLOGY AND MEDICINE, 2006, 40 (09) :1603-1614
[23]   Glucosamine/chondroitin combined with exercise for the treatment of knee osteoarthritis: a preliminary study [J].
Messier, S. P. ;
Mihalko, S. ;
Loeser, R. F. ;
Legault, C. ;
Jolla, J. ;
Pfruender, J. ;
Prosser, B. ;
Adrian, A. ;
Williamson, J. D. .
OSTEOARTHRITIS AND CARTILAGE, 2007, 15 (11) :1256-1266
[24]   The role of mesenchymal cells in the pathophysiology of inflammatory arthritis [J].
Meyer, Lars-Henrik ;
Franssen, Lars ;
Pap, Thomas .
BEST PRACTICE & RESEARCH IN CLINICAL RHEUMATOLOGY, 2006, 20 (05) :969-981
[25]   The fibroblast-like synovial cell in rheumatoid arthritis: a key player in inflammation and joint destruction [J].
Mor, A ;
Abramson, SB ;
Pillinger, MH .
CLINICAL IMMUNOLOGY, 2005, 115 (02) :118-128
[26]   EFFECT OF REACTIVE OXYGEN SPECIES ON THE BIOSYNTHESIS AND STRUCTURE OF NEWLY SYNTHESIZED PROTEOGLYCANS [J].
PANASYUK, A ;
FRATI, E ;
RIBAULT, D ;
MITROVIC, D .
FREE RADICAL BIOLOGY AND MEDICINE, 1994, 16 (02) :157-167
[27]   The lonely death: Chondrocyte apoptosis in TNF-induced arthritis [J].
Polzer, Karin ;
Schett, Georg ;
Zwerina, Jochen .
AUTOIMMUNITY, 2007, 40 (04) :333-336
[28]  
ROLLS A, 2005, FASEB J, P547
[29]   Caspase recruitment domain 15 mutations and rheumatic diseases [J].
Rose, CD ;
Martin, TM .
CURRENT OPINION IN RHEUMATOLOGY, 2005, 17 (05) :579-585
[30]   NF-κB:: a key role in inflammatory diseases [J].
Tak, PP ;
Firestein, GS .
JOURNAL OF CLINICAL INVESTIGATION, 2001, 107 (01) :7-11