Bacterial TIR domain-derived peptides inhibit innate immune signaling and catabolic responses in chondrocyte
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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.
KeywordsDecoy peptide Chondrocyte Innate immune signaling TLR pathway Catabolic responses
LH, SW, JG, YK, and WL designed the project. LH, SJ, XY, QY, XY, YW and YK performed the experiments. LH, SW, JG and WL analyzed the data. All authors were involved in writing and editing the paper. YW, YK and WL supervised all aspects of this work.
This work was financially supported by Beijing Municipal Natural Science Foundation (7174330), National Natural Science Foundation of China (30672133, 81671977, and 81301405) and National Key Research and Development Program of China (2016YFC1202905, 2018ZX10713003, 2018ZX10732401).
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Conflict of interest
The authors declare that they have no conflict of interest.
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