Overexpression of HMGB1 A-box reduced IL-1β-induced MMP expression and the production of inflammatory mediators in human chondrocytes
Overexpression of HMGB1 A-box reduced IL-1β-induced MMP expression and the production of inflammatory mediators in human chondrocytes
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DOI：
10.1016/j.yexcr.2016.10.014
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发表时间：
2016-11-15
影响因子：
3.7
通讯作者：
Lu, Daigang
中科院分区：
文献类型：
--
作者：
Fu, Yahui;Lei, Jinlai;Lu, Daigang
促炎细胞因子白细胞介素-1 β（IL-1 β）通过刺激几种有助于软骨降解的介质在骨关节炎（OA）的发病机制中起着至关重要的作用。本研究旨在探讨高迁移率族蛋白1（HMGB 1）抑制剂HMGB 1 A-box对IL-1 β激活的人骨关节炎软骨细胞基质金属蛋白酶（MMP）表达和炎症介质产生的影响及其机制。我们发现，HMGB 1 A box的过表达显著降低了IL-1 β刺激的MMP-1、MMP-3和MMP-9的产生，并且还降低了与抑制IL-1 β刺激的软骨细胞中前列腺素E2（PGE 2）和一氧化氮（NO）产生相关的诱导型一氧化氮合酶（iNOS）和环氧合酶-2（考克斯-2）的升高水平。此外，HMGB 1 A-box的过表达显著抑制了软骨细胞中由IL-1 β引起的ADAMTS-4、ADAMTS-5和HMGBI的上调。此外，HMGB 1 A-box的过表达显著抑制IL-1 β介导的Toll样受体4（TRL 4）/NF-κ B通路的激活。我们的观察表明，HMGB 1 A-box可以通过抑制IL-1 β诱导的MMPs表达而发挥保护作用，并且软骨细胞中炎症介质的产生与HMGB 1/TLR 4/NF-κ B通路的抑制有关。总之，HMGB 1 A-box缓解OA的发展，这可能与调节HMGB 1/TLR 4/NF-κ B通路有关。
The pro-inflammatory cytokine interleukin-1 beta (IL-1 beta) plays a crucial role in the pathogenesis of osteoarthritis (OA) by stimulating several mediators that contribute to cartilage degradation. The aim of this study was to investigate the effects and mechanism of high mobility group box 1 (HMGB1) inhibitors HMGB1 A-box on the expression of matrix metalloproteinase (MMP) and the production of inflammatory mediators in human osteoarthritis chondrocytes after activation by IL-1 beta. We found that the overexpression of HMGB1 A box significantly decreased the IL-1 beta-stimulated the production of MMP-1, MMP-3 and MMP-9, and also reduced the elevated levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) associated with the inhibition of prostaglandin E2 (PGE2) and nitric oxide (NO) production in IL-1 beta-stimulated chondrocytes. In addition, overexpression of the HMGB1 A-box significantly inhibited the up-regulation of ADAMTS-4, ADAMTS-5 and HMGBI caused by IL-1 beta in chondrocytes. Moreover, the overexpression of HMGB1 A-box markedly suppressed the IL-1 beta-mediated activation of the Toll-like receptor 4 (TRL4)/NF-kappa B pathway. Our observations indicated that the HMGB1 A-box can play a protective role by suppressing the IL-1 beta-induced expression of MMPs and that the production of inflammatory mediators in chondrocytes was associated with suppression of the HMGB1/TLR4/NF-kappa B pathway. In conclusion, HMGB1 A-box relieves the development of OA that may be associated with regulating the HMGB1/TLR4/NF-kappa B pathway.