The proteoglycan biglycan mediates inflammatory response by activating TLR-4 in human chondrocytes: Inhibition by specific siRNA and high polymerized Hyaluronan
The proteoglycan biglycan mediates inflammatory response by activating TLR-4 in human chondrocytes: Inhibition by specific siRNA and high polymerized Hyaluronan
复制标题
DOI：
10.1016/j.abb.2018.01.007
复制
发表时间：
2018-02-15
影响因子：
3.9
通讯作者：
Campo, Giuseppe M.
中科院分区：
文献类型：
--
作者：
Avenoso, Angela;D'Ascola, Angela;Campo, Giuseppe M.
软骨退化是关节软骨磨损、撕裂、机械和炎症损伤的标志。组织降解以及损害器官的完整性和功能，产生不同的中间产物，直接能够刺激进一步的炎症作用，从而放大炎症反应。双糖蛋白聚糖是细胞外基质的可溶性组分，其在组织损伤期间释放。据报道，在某些细胞类型中，释放的双糖链是TLR-2/4的内源性配体。我们研究了双糖蛋白聚糖在人软骨细胞双糖蛋白聚糖诱导的炎症反应的实验模型中的作用，以及高聚合HA对降低其活性的作用。软骨细胞暴露于LPS产生细胞损伤，包括高水平的双糖蛋白聚糖。用双糖蛋白聚糖处理软骨细胞产生几种有害炎症介质如IL-1 β、IL-6、MMP-13和IL-17的高mRNA表达，以及NF-kB和TLR-4活化。给予暴露于双糖链蛋白聚糖的软骨细胞高聚合的HA能够通过降低炎症介质的表达来减弱炎症反应。TLR-4参与介导双糖链的作用已被特异性沉默剂（siRNA）证实，这些数据可用于开发新的抗炎方法。
Cartilage degeneration are hallmarks of wear, tear, mechanical and inflammatory damage of the joint cartilage. Tissue degradation as well as compromising the integrity and function of the organ, produces different intermediates, directly able to stimulate further inflammatory effect, therefore, amplifying the inflammation response. Biglycan is a soluble component of the extracellular matrix that is released during tissue injury. It has been reported that released biglycan is an endogenous ligand for TLR-2/4 in some cell type. We studied the role of biglycan in an experimental model of biglycan-induced inflammatory response in human chondrocytes and the effect of high polymerized HA on reducing its activity. Exposition of chondrocytes to LPS generated cell injury, including high levels of biglycan. Chondrocyte treatment with biglycan produces a high mRNA expression of several detrimental inflammation mediators such as IL-1 beta, IL-6, MMP-13, and IL-17, as well as NF-kB and TLR-4 activation. Administration of high polymerized HA to chondrocytes exposed to biglycan was able to attenuate the inflammatory response by decreasing the expression of the inflammatory mediators. Involvement of the TLR-4 in the mediation of the biglycan action was confirmed using a specific silent agent (siRNA).Taken together, these data could be used to develop new anti-inflammatory approaches.