Clonorchis sinensis excretory/secretory products promote the secretion of TNF-alpha in the mouse intrahepatic biliary epithelial cells via Toll-like receptor 4.
Clonorchis sinensis excretory/secretory products promote the secretion of TNF-alpha in the mouse intrahepatic biliary epithelial cells via Toll-like receptor 4.
复制标题
华支睾吸虫排泄/分泌产物通过Toll样受体4促进小鼠肝内胆管上皮细胞分泌TNF-α。
DOI：
10.1186/s13071-015-1171-0
复制
发表时间：
2015-10-24
影响因子：
3.2
通讯作者：
Zheng KY
中科院分区：
文献类型：
--
作者：
Yan C;Wang YH;Yu Q;Cheng XD;Zhang BB;Li B;Zhang B;Tang RX;Zheng KY
Toll样受体4（TLR 4）作为最重要的病原模式识别物（PPRs）之一，在诱导天然免疫和介导针对外源抗原的适应性应答中起着重要作用。然而，很少有人知道TLR 4的作用，在胆管上皮细胞（BECs）诱导的免疫反应的华支睾吸虫，在人类健康的重要寄生虫。本研究用TLR 4抑制肽或对照肽预处理原代小鼠肝内胆管上皮细胞（MIBECs），然后用C.中华绒螯蟹。分别采用Western blot和磁珠分析检测系统检测TLR 4和相关细胞因子的表达。结果表明，C.结果表明，与对照组相比，当归提取物可显著增加BECs中TLR 4的表达，从而促进MyD 88和NF-κB的表达; ESP单独刺激MIBECs后，MIBECs中TNF-α的水平也显著升高，但IL-6的水平无明显变化。而TLR 4抑制剂预处理后，MIBECs的TNF-α浓度明显降低。此外，ESP还能抑制LPS诱导的MIBECs分泌IL-6。我们的数据首次证明了C.结论：中华绒螯蟹能通过TLR 4诱导MIBECs分泌促炎性细胞因子，提示TLR 4在宿主抗C.中华华支睾吸虫病的发病机制。
Toll-like receptor 4 (TLR4), as one of the most important pathogen pattern recognitions (PPRs) plays a central role in elicitation of innate immunity and mediation of adaptive responses against foreign antigens. However, little is known of the roles of TLR4 in the immune responses of biliary epithelial cells (BECs) induced by Clonorchis sinensis, a parasite of significance in human health. In the present study, the primary mouse intrahepatic biliary epithelial cells (MIBECs) were pre-treated with TLR4 inhibitor peptide or control peptide and then stimulated by excretory/secretory products (ESP) of C. sinensis, respectively. The expressions of TLR4 and relative cytokines were determined using western blot and a bead-based analytic detection system, respectively. The results showed that ESP of C. sinensis significantly increased the expression of TLR4 which promoted the expression of MyD88 and NF-κB in BECs; the levels of TNF-α but not IL-6 from MIBECs stimulated by ESP alone were also considerably increased, compared with the group of the medium stimulated. However, the concentration of TNF-α was significantly decreased when MIBECs were pre-treated with TLR4 inhibitor. In addition, ESP could depress the level of IL-6 in MIBECs which was elevated by LPS. Our data for the first time demonstrate that ESP of C. sinensis can potently induce secretion of pro-inflammatory cytokines via TLR4 in MIBECs, which suggests that TLR4 plays an important role in host defenses against C. sinensis and the pathogenesis of clonorchiasis.