Hyaluronan in part mediates IL-1beta-induced inflammation in mouse chondrocytes by up-regulating CD44 receptors

被引:37
作者
Campo, Giuseppe M. [1 ]
Avenoso, Angela [1 ]
D'Ascola, Angela [1 ]
Scuruchi, Michele [1 ]
Prestipino, Vera [1 ]
Calatroni, Alberto [1 ]
Campo, Salvatore [1 ]
机构
[1] Univ Messina, Dept Biochem Physiol & Nutr Sci, Sch Med, Policlin Univ,Sect Med Chem, I-98125 Messina, Italy
关键词
Hyaluronan; NF-kB; Cytokines; CD44; Hyaluronidase; MMP-13; EXTRACELLULAR-MATRIX; IMMUNE-RESPONSE; KAPPA-B; FRAGMENTS; INTERLEUKIN-1-BETA; OSTEOARTHRITIS; HEALTH; INJURY;
D O I
10.1016/j.gene.2011.11.064
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Interleukin-1beta (IL-1beta) elicits the expression of inflammatory mediators through a mechanism involving the CD44 receptor. Hyaluronan (HA) depolymerization also contributes to CD44 activation. This study investigated the potential of HA fragments, obtained by hyaluronidase (HYAL) treatment, as mediators of CD44 activation on IL-1beta-induced inflammation in mouse chondrocytes. mRNA and related protein levels were measured for CD44, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), matrix metalloproteinase-13 (MMP-13) and inducible nitric oxide synthase (iNOS) in chondrocytes, treated or untreated with IL-1beta, either with or without the addition of HYAL The level of NF-kB activation was also assayed. CD44 mRNA expression was higher than controls in chondrocytes treated with IL-1beta. IL-1beta also induced NF-kB up-regulation and increased TNF-alpha, IL-6, MMP-13 and iNOS expression. Different effects resulted from HYAL treatment. Treatment of chondrocytes exposed to IL-1beta with HYAL synergistically increased the same parameters up-regulated by IL-1beta, while the same parameters were increased by HYAL in chondrocytes not exposed to IL-1beta but to a lesser extent. Specific CD44 blocking antibody and hyaluronan binding protein (HABP), which inhibit HA activity, were used to confirm CD44 to be the target of IL-1beta action through HA mediation. HA levels and molecular size further confirm the role of degraded HA. These findings suggest that IL-1beta exerts inflammatory activity via CD44 by the mediation of HA fragments derived from HA depolymerization. (C) 2011 Elsevier B.V. All rights reserved.
引用
收藏
页码:24 / 35
页数:12
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