Chen Qianbo, Hou Tianyong, Wu Xuehui, Luo Fei, Xie Zhao, Xu Jianzhong
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.
Inflammation. 2016 Apr;39(2):798-806. 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.
骨髓炎是侵袭性金黄色葡萄球菌感染的常见表现，其特征是广泛的骨质流失和破坏。吞噬细胞拥有多种检测病原体的受体，包括Toll样受体（TLR）。先前的研究表明，金黄色葡萄球菌蛋白SpA通过肿瘤坏死因子受体-1（TNFR-1）直接与前成骨细胞结合。在我们目前的研究中，我们研究了金黄色葡萄球菌感染的成骨细胞中TLR2和TNFR-1之间的关系。我们的结果表明，随着金黄色葡萄球菌浓度的增加，细胞活力下降，细胞凋亡、TLR2的表达以及炎性细胞因子（TNF-α和IL-6）的分泌增加。JNK通路也因金黄色葡萄球菌感染而被激活。敲低TNFR1不仅抑制了JNK通路，还降低了金黄色葡萄球菌感染细胞中TLR2蛋白和RANKL水平。抑制JNK通路降低了金黄色葡萄球菌感染细胞中TLR2的蛋白水平，并减少了TNF-α和IL-6的分泌。
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