Bacterium-induced CXCL10 secretion by osteoblasts can be mediated in part through toll-like receptor 4
Bacterium-induced CXCL10 secretion by osteoblasts can be mediated in part through toll-like receptor 4
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DOI：
10.1128/iai.70.8.4075-4082.2002
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发表时间：
2002-08-01
影响因子：
3.1
通讯作者：
Bost, KL
中科院分区：
文献类型：
--
作者：
Gasper, NA;Petty, CC;Bost, KL
研究了已知引起骨感染的两种常见病原体沙门氏菌和金黄色葡萄球菌，以确定它们在培养的小鼠和人成骨细胞中诱导趋化因子表达的能力。虽然这些细胞负责骨形成，但我们惊讶地发现它们可以通过上调趋化因子CXCL 10（IP-10）的表达来响应细菌感染。而革兰氏阴性菌沙门氏菌和革兰氏阳性菌S.金黄色葡萄球菌诱导CXCL 10的表达。逆转录-PCR和酶联免疫吸附分析分别显示沙门氏菌诱导的CXCL 10 mRNA和蛋白表达水平高，而成骨细胞对沙门氏菌的反应。与这些发现一致，沙门氏菌衍生的脂多糖（LPS），而不是S。金黄色葡萄球菌来源的肽聚糖可以诱导CXCL 10的表达。针对Toll样受体4（TLR 4）的抗体可以阻断LPS诱导的CXCL 10产生，证明成骨细胞功能性表达TLR 4。尽管细菌感染的成骨细胞的TLR 2 mRNA表达的诱导性质，肽聚糖未能刺激CXCL 10分泌。细菌感染的颅骨的免疫荧光染色（即，颅骨）证实成骨细胞中存在CXCL 10。成骨细胞不表达CXCR 3 mRNA，而T淋巴细胞可以表达高水平的这种受体，这一事实表明，成骨细胞衍生的CXCL 10可能会招募T淋巴细胞到骨感染的部位。
Two common pathogens known to cause bone infection, Salmonella and Staphylococcus aureus, were investigated to determine their abilities to induce chemokine expression in cultured mouse and human osteoblasts. While these cells are responsible for bone formation, we were surprised to find that they could respond to bacterial infection by upregulating expression of the chemokine CXCL10 (IP-10). However, there were significant differences in the abilities of the gram-negative bacterium Salmonella and the gram-positive bacterium S. aureus to induce expression of CXCL10. Reverse transcription-PCR and enzyme-linked immunosorbent assay analyses showed high levels of Salmonella-induced CXCL10 mRNA and protein expression, respectively, whereas the osteoblast response to S. aureus was significantly less. Consistent with these findings, Salmonella-derived lipopolysaccharide (LPS), but not S. aureus-derived peptidoglycan, could induce expression of CXCL10. An antibody against toll-like receptor 4 (TLR4) could block the LPS-induced CXCL10 production, demonstrating the functional expression of TLR4 by osteoblasts. Despite the inducible nature of TLR2 mRNA expression by bacterium-infected osteoblasts, peptidoglycan failed to stimulate CXCL10 secretion. Immunofluorescent staining of bacterium-infected calvaria (i.e., skull bone) demonstrated the presence of CXCL10 in osteoblasts. The fact that osteoblasts did not express CXCR3 mRNA, whereas T lymphocytes can express high levels of this receptor, suggests that osteoblast-derived CXCL10 may recruit T lymphocytes to the sites of bone infections.