Bacterial TIR domain-derived peptides inhibit innate immune signaling and catabolic responses in chondrocyte
Bacterial TIR domain-derived peptides inhibit innate immune signaling and catabolic responses in chondrocyte
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细菌 TIR 结构域衍生肽抑制软骨细胞的先天免疫信号和分解代谢反应
DOI：
10.1007/s11033-019-04627-8
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发表时间：
2019-03
影响因子：
2.8
通讯作者：
Li Wenfeng
中科院分区：
文献类型：
--
作者：
Hong Lei;Wang Shijie;Guo Jinpeng;Yin Xin;Yu Qianjin;Yang Mingjuan;Wang Yufei;Ke Yuehua;Li Wenfeng
骨关节炎（OA）是一种退行性关节疾病，其中低度炎症在起始步骤中起重要作用。低剂量的LPS诱导的炎症在血浆中激活软骨细胞并促进促炎细胞因子的分泌，导致继发性炎症。阻断OA相关的TLR激活是开发合适疗法的有前景的策略。在这里，我们希望找到一些细菌来源的肽，可以更有效地阻断软骨细胞中的TLR信号。在前人研究的基础上，我们筛选了12个TIR结构域衍生肽对LPS、IL-1 β或TNF-α诱导的小鼠ATDC-5细胞NF-B活化的影响。我们评估了它们对LPS诱导的细胞因子表达和分泌的影响。其中，TcpC-DD和TcpB-DD两种细菌源肽的抑制活性最强。与TcpB-DD相比，TcpC-DD在软骨细胞炎症过程中表现出更广泛的TLR抑制特异性。此外，TcpC-DD和TcpB-DD对LPS和IL-1 β诱导的软骨细胞分解代谢反应均有较强的抑制作用。但只有TcpC-DD对TNF-α诱导的细胞增殖有明显的抑制作用。总之，我们确定了两个新的抑制肽，调节软骨细胞和先天免疫反应中的catalysts，这些肽可用于开发新的治疗策略OA。
Osteoarthritis (OA) is a degenerative joint disease, in which low-grade inflammation plays an important role at the initiating step. Low-doses of LPS-induced inflammation in the plasma activate chondrocytes and promote the secretion proinflammatory cytokines, leading to secondary inflammation. Blocking OAassociated TLR activation is a promising strategy for the development of suitable therapies. Here, we want to find some bacteria-derived peptides that can block TLR signaling in chondrocytes more efficiently. Based on previous studies, we screened 12 TIR domain-derived peptides for their effects on NF-кB activation induced by LPS, IL-1β or TNF-α in murine ATDC-5 cells. We evaluated their effects on LPS-induced cytokine expression and secretion. Among them, two bacteria-derived peptides, TcpC-DD and TcpB-DD, showed the most potent inhibitory activities. In comparison with TcpB-DD, TcpC-DD exhibited broader TLR-inhibitory specificity during inflammation in chondrocytes. Furthermore, both TcpC-DD and TcpB-DD displayed strong inhibition of LPS- and IL-1β-induced catabolic reactions in chondrocytes. However, only TcpC-DD exhibited obvious suppression of TNF-α-induced catabolism. In conclusion, we identified two novel inhibitory peptides that modulate catabolism in chondrocytes and innate immune responses, and these peptides could be used to develop novel therapeutic strategies for OA.
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影响因子：
5.3
作者：
Miller, Michelle A.;McTernan, Philip G.;Cappuccio, Francesco P.
通讯作者：
Cappuccio, Francesco P.
影响因子：
4.9
作者：
Mullen LM;Chamberlain G;Sacre S
通讯作者：
Sacre S
影响因子：
4.4
作者：
Toshchakov, Vladimir Y.;Fenton, Matthew J.;Vogel, Stefanie N.
通讯作者：
Vogel, Stefanie N.
DOI：
10.1073/pnas.1313575110
发表时间：
2013-11-19
影响因子：
11.1
作者：
Piao, Wenji;Ru, Lisa W.;Toshchakov, Vladimir Y.
通讯作者：
Toshchakov, Vladimir Y.
DOI：
10.1038/nrrheum.2015.158
发表时间：
2016-02
期刊：
Nature reviews. Rheumatology
影响因子：
--
作者：
Huang Z;Kraus VB
通讯作者：
Kraus VB