PMID- 31610189 OWN - NLM STAT- MEDLINE DCOM- 20191217 LR - 20191217 IS - 1879-0631 (Electronic) IS - 0024-3205 (Linking) VI - 238 DP - 2019 Dec 1 TI - Dendritic cells aggregate inflammation in experimental osteoarthritis through a toll-like receptor (TLR)-dependent machinery response to challenges. PG - 116920 LID - S0024-3205(19)30847-1 [pii] LID - 10.1016/j.lfs.2019.116920 [doi] AB - AIMS: Dendritic cells (DCs) and Toll-like receptor (TLR) participate in mediating inflammation process. However, the functional role of TLR expressed on DCs in osteoarthritis (OA) development has not been defined yet. The purpose of this study was to investigate the role and mechanism of TLR and DCs in the progression of experimental osteoarthritis (OA). MATERIALS AND METHODS: Experimental OA model was induced by iodoacetate injection. Expressions of toll-like receptors in DCs of OA mice were detected by qRT-PCR and flow cytometry. TLR agonists lipopolysaccharide (LPS) and R848 or TLR antagonist FP7 were used, and the levels of TLRs and inflammatory cytokines were examined by qRT-PCR and ELISA. KEY FINDINGS: The expression levels of TLR family members were increased in DCs derived from synovial fluid of OA mice compared with the sham mice. In vitro, OA mice-derived DCs had increased production of inflammatory cytokine after TLR agonists LPS and R848 challenge, while TLR challenges did not affect DCs maturation. Inhibition of TLR by TLR antagonist FP7 blocked TLR challenges-induced increased inflammation in DCs. In mice, administration of FP7 attenuated LPS-induced inflammatory response and OA condition. SIGNIFICANCE: Increased TLR expression in OA-derived DCs contributes to the inflammation condition and potentially acts as a therapeutic target for osteoarthritis. CI - Copyright (c) 2019 Elsevier Inc. All rights reserved. FAU - Nie, Fengfeng AU - Nie F AD - Department of Orthopedics, Linyi Central Hospital, Linyi, Shandong, 276400, China. FAU - Ding, Fei AU - Ding F AD - Department of Orthopedics, Sheyang County People's Hospital, Yancheng, Jiangsu, 224300, China. FAU - Chen, Bo AU - Chen B AD - Department of Orthopedics, Linyi Central Hospital, Linyi, Shandong, 276400, China. FAU - Huang, Shouguo AU - Huang S AD - Department of Orthopedics, Linyi Central Hospital, Linyi, Shandong, 276400, China. FAU - Liu, Qingbai AU - Liu Q AD - Department of Orthopedics, Lianshui County People's Hospital, The Affiliated Lianshui County People's Hospital of Kangda College of Nanjing Medical University, Huai'an, Jiangsu, 223400, China. Electronic address: liu678vip@163.com. FAU - Xu, Changming AU - Xu C AD - Department of Orthopedics, Lianshui County People's Hospital, The Affiliated Lianshui County People's Hospital of Kangda College of Nanjing Medical University, Huai'an, Jiangsu, 223400, China. Electronic address: sea009@126.com. LA - eng PT - Journal Article DEP - 20191011 PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - 0 (Cytokines) RN - 0 (Lipopolysaccharides) RN - 0 (Toll-Like Receptors) SB - IM MH - Animals MH - Arthritis, Rheumatoid/*complications MH - Cytokines/metabolism MH - Dendritic Cells/*immunology/metabolism MH - Inflammation/*etiology/metabolism/pathology MH - Lipopolysaccharides/toxicity MH - Mice MH - Mice, Inbred C57BL MH - Osteoarthritis/*complications MH - Toll-Like Receptors/*metabolism OTO - NOTNLM OT - Dendritic cells OT - Inflammation OT - Osteoarthritis OT - Toll-like receptor EDAT- 2019/10/15 06:00 MHDA- 2019/12/18 06:00 CRDT- 2019/10/15 06:00 PHST- 2019/08/16 00:00 [received] PHST- 2019/09/26 00:00 [revised] PHST- 2019/09/27 00:00 [accepted] PHST- 2019/10/15 06:00 [pubmed] PHST- 2019/12/18 06:00 [medline] PHST- 2019/10/15 06:00 [entrez] AID - S0024-3205(19)30847-1 [pii] AID - 10.1016/j.lfs.2019.116920 [doi] PST - ppublish SO - Life Sci. 2019 Dec 1;238:116920. doi: 10.1016/j.lfs.2019.116920. Epub 2019 Oct 11.