Double-stranded RNA released from damaged articular chondrocytes promotes cartilage degeneration via Toll-like receptor 3-interleukin-33 pathway.
Double-stranded RNA released from damaged articular chondrocytes promotes cartilage degeneration via Toll-like receptor 3-interleukin-33 pathway.
复制标题
受损关节软骨细胞释放的双链 RNA 通过 Toll 样受体 3-interleukin-33 途径促进软骨退化
DOI：
10.1038/cddis.2017.534
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发表时间：
2017-11-02
影响因子：
9
通讯作者：
Deng L
中科院分区：
文献类型：
--
作者：
Li C;Chen K;Kang H;Yan Y;Liu K;Guo C;Qi J;Yang K;Wang F;Guo L;He C;Deng L
包括Toll样受体3(TLR3)在内的模式识别受体(PRRs)参与了关节炎症反应，但白细胞介素33(IL-33)是否参与TLR3介导的软骨退变尚不清楚。在这里，我们发现IL-33在骨性关节炎的软骨细胞中大量增加，尤其是承重软骨的软骨细胞。此外，机械牵拉损伤关节软骨细胞释放的双链核糖核酸上调IL-33表达的程度大于IL-1β和肿瘤坏死因子-α。双链RNA通过TLR3-p38丝裂原活化蛋白激酶-核因子-κB(NF-κB)途径诱导IL-33表达。此外，p65和过氧化体增殖物激活受体-γ转录复合体的形成是双链RNA诱导IL-33表达所必需的。IL-33反过来作用于软骨细胞，诱导基质金属蛋白酶-1/13，抑制II型胶原的表达。这些发现表明，受损关节软骨细胞释放的dsRNA通过TLR3-IL-33途径促进软骨退变。
Pattern recognition receptors (PRRs), including Toll-like receptor 3 (TLR3), are involved in arthritic responses; however, whether interleukin-33 (IL-33) is involved in TLR3-mediated cartilage degeneration is unknown. Here, we found that IL-33 was abundantly increased in chondrocytes of osteoarthritis, especially the chondrocytes of weight-bearing cartilage. Furthermore, double-stranded RNA (dsRNA) released from damaged articular chondrocytes induced by mechanical stretching upregulated IL-33 expression to a greater degree than IL-1β and tumor necrosis factor-α. dsRNA induced IL-33 expression via the TLR3-p38 mitogen-activated protein kinase-nuclear factor-κB (NF-κB) pathway. In addition, formation of the p65 and peroxisome proliferator-activated receptor-γ transcriptional complex was required for dsRNA-induced IL-33 expression. IL-33, in turn, acted on chondrocytes to induce matrix metalloproteinase-1/13 and inhibit type II collagen expression. These findings reveal that dsRNA released from damaged articular chondrocytes promotes cartilage degeneration via the TLR3-IL-33 pathway.
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DOI：
10.1016/j.clim.2012.12.011
发表时间：
2013-03
期刊：
Clinical immunology (Orlando, Fla.)
影响因子：
--
作者：
Haseeb A;Haqqi TM
通讯作者：
Haqqi TM
Interleukin-33 通过激活皮肤中的诱导型一氧化氮合酶来增强抗菌防御
影响因子：
6.7
作者：
Li C;Li H;Jiang Z;Zhang T;Wang Y;Li Z;Wu Y;Ji S;Xiao S;Ryffel B;Radek KA;Xia Z;Lai Y
通讯作者：
Lai Y
影响因子：
168.9
作者：
Glyn-Jones, S.;Palmer, A. J. R.;Carr, A. J.
通讯作者：
Carr, A. J.
影响因子：
--
作者：
Brentano, F;Schorr, O;Kyburz, D
通讯作者：
Kyburz, D
影响因子：
7
作者：
Glasson, S. S.;Blanchet, T. J.;Morris, E. A.
通讯作者：
Morris, E. A.