Glycosaminoglycans reduced inflammatory response by modulating toll-like receptor-4 in LPS-stimulated chondrocytes
Glycosaminoglycans reduced inflammatory response by modulating toll-like receptor-4 in LPS-stimulated chondrocytes
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DOI：
10.1016/j.abb.2009.09.017
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发表时间：
2009-11-01
影响因子：
3.9
通讯作者：
Calatroni, Alberto
中科院分区：
文献类型：
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作者：
Campo, Giuseppe M.;Avenoso, Angela;Calatroni, Alberto
脂多糖（LPS）介导的toll样受体-4 （TLR-4）复合物的激活可诱导特异性信号通路，如髓样分化主要反应蛋白-88 （MyD88）和肿瘤坏死因子受体相关因子-6 (TRAF-6)，涉及nf - κ B的激活。由于先前的数据报道透明质酸（HA）和硫酸肝素（HS）可能与TLR-4相互作用，本研究的目的是研究糖胺聚糖（GAGs）是否可能在lps诱导的小鼠软骨细胞炎症因子模型中调节TLR-4受体。LPS刺激上调了所有炎症参数。GAG治疗产生多种作用：HA仅在高剂量时降低MyD88、TRAF-6水平和NF-kappa B激活，抗炎作用很低；硫酸软骨素（C4S）和硫酸软骨素（6-硫酸软骨素）显著抑制MyD88、TRAF-6和NF-kappa B的激活、炎症因子和诱导型一氧化氮合酶；HS与C4S一样，显著降低MyD88、TRAF-6、nf - κ B及炎症反应。特异性TLR-4阻断抗体证实TLR-4是GAG作用的靶点。(C) 2009爱思唯尔公司版权所有。
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-kappa B 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-kappa B 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-kappa B activation, the inflammation cytokines, and inducible nitric oxide synthase; HS, like C4S, significantly reduced MyD88, TRAF-6, NF-kappa B and inflammation. Specific TLR-4 blocking antibody confirmed that TLR-4 was the target of GAG action. (C) 2009 Elsevier Inc. All rights reserved.