title: Knockdown of TNFR1 Suppresses Expression of TLR2 in the Cellular Response to Staphylococcus aureus Infection.
abstract: Osteomyelitis is a common manifestation of invasive Staphylococcus aureus infection characterized by widespread bone loss and destruction. Phagocytes possess various receptors to detect pathogens, including the Toll-like receptors (TLRs). Previous studies have demonstrated that the S. aureus protein SpA binds directly to pre-osteoblastic cells via tumor necrosis factor receptor-1 (TNFR-1). In our present study, we investigated the relationship between TLR2 and TNFR-1 in S. aureus-infected osteoblasts. Our results showed that cell viability decreased, and apoptosis, expression of TLR2, and the secretion of inflammatory cytokines (TNF-α and IL-6) increased with increasing concentrations of S. aureus. The JNK pathway was also activated in response to S. aureus infection. Knockdown of TNFR1 not only inhibited the JNK pathway but also reduced TLR2 protein and RANKL levels in S. aureus-infected cells. Inhibition of the JNK pathway reduced the protein level of TLR2 and reduced TNF-α and IL-6 secretion in S. aureus-infected cells.
authors: National and Local United Engineering Laboratory of Tissue Engineering, Department of Orthopaedics, Southwest Hospital, The Third Military Medical University, Chongqing, China.|Key Laboratory of Bone Tissue Engineering in PLA, The Third Military Medical University, Chongqing, China.|Laboratory of Tissue Engineering in Chongqing City, Chongqing, China.|Center of Regenetive and Reconstructive Engineering Technology in Chongqing City, Chongqing, China.|Department of Orthopedics, 155 Hospital of PLA, Kaifeng, China.
authors: Qianbo
authors: Q
authors: Chen
authors: National and Local United Engineering Laboratory of Tissue Engineering, Department of Orthopaedics, Southwest Hospital, The Third Military Medical University, Chongqing, China. tianyonghou@126.com.|Key Laboratory of Bone Tissue Engineering in PLA, The Third Military Medical University, Chongqing, China. tianyonghou@126.com.|Laboratory of Tissue Engineering in Chongqing City, Chongqing, China. tianyonghou@126.com.|Center of Regenetive and Reconstructive Engineering Technology in Chongqing City, Chongqing, China. tianyonghou@126.com.
authors: Tianyong
authors: T
authors: Hou
authors: National and Local United Engineering Laboratory of Tissue Engineering, Department of Orthopaedics, Southwest Hospital, The Third Military Medical University, Chongqing, China.|Key Laboratory of Bone Tissue Engineering in PLA, The Third Military Medical University, Chongqing, China.|Laboratory of Tissue Engineering in Chongqing City, Chongqing, China.|Center of Regenetive and Reconstructive Engineering Technology in Chongqing City, Chongqing, China.
authors: Xuehui
authors: X
authors: Wu
authors: National and Local United Engineering Laboratory of Tissue Engineering, Department of Orthopaedics, Southwest Hospital, The Third Military Medical University, Chongqing, China.|Key Laboratory of Bone Tissue Engineering in PLA, The Third Military Medical University, Chongqing, China.|Laboratory of Tissue Engineering in Chongqing City, Chongqing, China.|Center of Regenetive and Reconstructive Engineering Technology in Chongqing City, Chongqing, China.
authors: Fei
authors: F
authors: Luo
authors: National and Local United Engineering Laboratory of Tissue Engineering, Department of Orthopaedics, Southwest Hospital, The Third Military Medical University, Chongqing, China.|Key Laboratory of Bone Tissue Engineering in PLA, The Third Military Medical University, Chongqing, China.|Laboratory of Tissue Engineering in Chongqing City, Chongqing, China.|Center of Regenetive and Reconstructive Engineering Technology in Chongqing City, Chongqing, China.
authors: Zhao
authors: Z
authors: Xie
authors: National and Local United Engineering Laboratory of Tissue Engineering, Department of Orthopaedics, Southwest Hospital, The Third Military Medical University, Chongqing, China. xjzslw@163.com.|Key Laboratory of Bone Tissue Engineering in PLA, The Third Military Medical University, Chongqing, China. xjzslw@163.com.|Laboratory of Tissue Engineering in Chongqing City, Chongqing, China. xjzslw@163.com.|Center of Regenetive and Reconstructive Engineering Technology in Chongqing City, Chongqing, China. xjzslw@163.com.
authors: Jianzhong
authors: J
authors: Xu
mesh_terms: D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival; D015850:Interleukin-6 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D010006:Osteoblasts / Q000382:microbiology / Q000473:pathology; D010019:Osteomyelitis / Q000382:microbiology / Q000473:pathology*; D053245:RANK Ligand / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000378:metabolism*; D013203:Staphylococcal Infections / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D013211:Staphylococcus aureus / Q000276:immunology / Q000472:pathogenicity*; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D053245:RANK Ligand; D034741:RNA, Small Interfering; D047888:Receptors, Tumor Necrosis Factor, Type I; C493486:Tlr2 protein, mouse; C506236:Tnfrsf1a protein, mouse; C505689:Tnfsf11 protein, mouse; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; D048031:JNK Mitogen-Activated Protein Kinases
keywords: JNK pathway; Staphylococcus aureus; Toll-like receptor 2; osteomyelitis; tumor necrosis factor receptor-1