中文摘要：

细菌脂多糖（LPS）可诱导宿主对LPS的耐受，但对细菌脂蛋白（BLP）是否存在交叉耐受，目前报道不一。采用人单核细胞株（THP-1），建立小剂量LPS诱导THP-1对LPS耐受的细胞模型；观察细胞肌动蛋白骨架、炎症因子TNF-α、IL-1β、IL-6的浓度及NF-κB的DNA结合活力的变化情况；探讨BLP交叉耐受及细胞骨架在其中的作用。结果显示，THP-1细胞经小剂量（10ng／m1）LPS、大剂量（100ng／m1）LPS或BLP刺激后，细胞形态严重变形，肌动蛋白重组，细胞周边肌动蛋白丝带消失，出现明显的肌动蛋白收缩团块及伪足，细胞核内NF-κB的DNA结合活性显著升高，培养上清液中炎症因子（TNF-α、IL-1β及IL-6）的释放显著增加；而小剂量LPS预刺激12h后，再用大剂量的LPS或BLP刺激6h，上述指标明显改善；采用细胞骨架肌动蛋白聚集破坏剂鬼笔环肽预处理后的THP-1细胞，可取消由小剂量LPS诱导的自身耐受及对BLP的交叉耐受；可见，细菌LPS、BLP（100ng／m1）可诱导THP-1细胞肌动蛋白骨架的改变，激活NF-κB信号通路，诱导炎性细胞因子TNF-α、IL-1、IL-6过度释放，激活宿主炎症细胞的炎症反应：而小剂量LPS预刺激后可诱导出THP-1细胞对LPS的自身耐受和对BLP的交叉耐受；细胞骨架肌动蛋白参与了小剂量LPS诱导THP-1细胞对LPS自身耐受和对BLP交叉耐受的形成。

英文摘要：

Abstract It is remain uncertain whether bacterial lipopolysaccharide （LPS）-toleranced monocyte cross-toleranced with bacterial lipoprotein （BLP）. The study was aimed to observe the LPS tolerance and BLP cross-tolerance induced by LPS （10 ng/ml） and the changes of actin, and to explore the role of actin cytoskeleton in LPS-tolerance and BLP cross-tolerance in THP-1. The human monocyte cell line （THP-1） were adopted to establish the LPS-toleranced and BLP cross-toleranced cellular models. Actin skeleton, supernatant concentration of cytokins （TNF-α, IL-1β and IL-6） and NF-κB DNA binding activity was tested. When THP-1 were insulted with LPS （100 ng/ml） or BLP （100 ng/ml）, The cellular morphologic changes were significant with the formation of pseudopod and the actin reorganized to form the actin-band, NF-κB DNA binding activity upregulated in nuclear, and the concentration of cytokins （TNF-α, IL-1β and IL-6） in supernatant increased in THP-1. Pretreatment THP-1 with LPS （10 ng/ ml）, the morphology, cytokines and NF-κB DNA binding activity were improved. Phalladin, a specifical actin cytoskeleton reorganization inhibitor, party abolished the LPS tolerance and BLP cross-tolerance in THP- 1 cell induced by 10 ng/ml LPS. The results suggested that LPS （100 ng/ml） and BLP （100 ng/ml） could trigger the reorganization of actin cytoskeleton, activate NF-κB transcription, and increase the cytokins （TNF-α, IL- 1β and IL-6） releasing, which were closely associated with the activatation of inflammation. LPS （10 ng/ml） pretreatment could induce LPS tolerance and BLP cross-tolerance in THP-1 which was at least partly associated with actin cytoskeleton.