Knockdown of TNFR1 Suppresses Expression of TLR2 in the Cellular Response to Staphylococcus aureus Infection

• Published in: Inflammation 2016-04, Vol.39 (2), p.798-806
• Main Authors: Chen, Qianbo, Hou, Tianyong, Wu, Xuehui, Luo, Fei, Xie, Zhao, Xu, Jianzhong
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Animals; Apoptosis - physiology; Biomedical and Life Sciences; Biomedicine; Cell Line; Cell Survival; Immunology; Interleukin-6 - secretion; Internal Medicine; JNK Mitogen-Activated Protein Kinases - antagonists & inhibitors; JNK Mitogen-Activated Protein Kinases - metabolism; MAP Kinase Signaling System; Mice; Original Article; Osteoblasts - microbiology; Osteoblasts - pathology; Osteomyelitis - microbiology; Osteomyelitis - pathology; Pathology; Pharmacology/Toxicology; RANK Ligand - metabolism; Receptors, Tumor Necrosis Factor, Type I - genetics; Receptors, Tumor Necrosis Factor, Type I - metabolism; Rheumatology; RNA Interference; RNA, Small Interfering - genetics; Staphylococcal Infections - immunology; Staphylococcal Infections - microbiology; Staphylococcal Infections - pathology; Staphylococcus aureus; Staphylococcus aureus - immunology; Staphylococcus aureus - pathogenicity; Toll-Like Receptor 2 - biosynthesis; Toll-Like Receptor 2 - metabolism; Tumor Necrosis Factor-alpha - secretion
• ISSN: 0360-3997; 1573-2576
• DOI: 10.1007/s10753-016-0308-4

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.