Lipopolysaccharide Upregulated Intestinal Epithelial Cell Expression of Fn14 and Activation of Fn14 Signaling Amplify Intestinal TLR4-Mediated Inflammation.
Lipopolysaccharide Upregulated Intestinal Epithelial Cell Expression of Fn14 and Activation of Fn14 Signaling Amplify Intestinal TLR4-Mediated Inflammation.
复制标题
脂多糖上调肠上皮细胞 Fn14 表达并激活 Fn14 信号放大肠道 TLR4 介导的炎症
DOI：
10.3389/fcimb.2017.00315
复制
发表时间：
2017
影响因子：
5.7
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Qi X;Qin L;Du R;Chen Y;Lei M;Deng M;Wang J
在肠上皮细胞中，TLR4在与其同源配体脂多糖（LPS）结合后显示出炎症和体内平衡的作用。TWEAK-Fn14轴在过度或异常炎症反应引起的病理中起重要作用。本研究旨在探讨猪小肠上皮细胞中TLR4和TWEAK/Fn14系统之间可能存在的串扰。我们的体内实验结果显示，与同龄正常对照仔猪相比，LPS刺激仔猪小肠上皮中Fn14表达增加，固有层中TWEAK表达降低。与此发现一致的是，LPS处理增加了猪小肠上皮细胞系SIEC02中Fn14和TLR4的表达，而降低了TWEAK的表达。有趣的是，使用激动性抗Fn14来调节Fn14的激活可以减少SIEC02介导的tlr4介导的TNF-α的产生。此外，重组TWEAK蛋白预处理LPS刺激的SIEC02可抑制Fn14和TNF-α的表达，抑制LPS对紧密连接蛋白occludin表达的负面影响。综上所述，本研究表明，与tweak无关的Fn14激活增强了仔猪肠道中tlr4介导的炎症反应。此外，tweak依赖性的Fn14信号抑制可能在肠道内稳态中发挥作用。
TLR4 in intestinal epithelial cells has been shown both inflammatory and homeostatic roles following binding of its cognate ligand lipopolysaccharide (LPS). TWEAK-Fn14 axis plays an important role in pathologies caused by excessive or abnormal inflammatory responses. This study aimed to evaluate potential cross-talk between TLR4 and TWEAK/Fn14 system in porcine small intestinal epithelial cells. Our in vivo results showed that, compared with the age-matched normal control piglets, increased expression of Fn14 in epithelium and decreased TWEAK expression in lamina propria were detected in the small intestinal of piglets stimulated with LPS. Consistent with this finding, treatment with LPS increased the expression of Fn14 and TLR4 while decreased TWEAK expression in porcine small intestinal epithelial cell lines SIEC02. Interestingly, modulating Fn14 activation using agonistic anti-Fn14 decreased TLR4-mediated TNF-α production by SIEC02. In addition, pretreatment of LPS-stimulated SIEC02 with recombinant TWEAK protein suppresses the expression of Fn14 and TNF-α and inhibits the negative impact of LPS on the tight junctional protein occludin expression. In conclusion, this study demonstrates that the TWEAK-independent Fn14 activation augments TLR4-mediated inflammatory responses in the intestine of piglets. Furthermore, the TWEAK-dependent suppression of Fn14 signaling may play a role in intestinal homeostasis.
登录
查看更多内容
影响因子：
4.4
作者：
Fernandes, Philana;O'Donnell, Charlotte;Houston, Aileen
通讯作者：
Houston, Aileen
影响因子：
4.8
作者：
Fotin-Mleczek, M;Henkler, F;Wajant, H
通讯作者：
Wajant, H
影响因子：
20.3
作者：
Chopra, Martin;Brandl, Andreas;Wajant, Harald
通讯作者：
Wajant, Harald
日粮甘氨酰谷氨酰胺对脂多糖攻击的断奶仔猪生长性能、小肠完整性和免疫反应的影响
影响因子：
3.3
作者：
Jiang, Z. Y.;Sun, L. H.;Zou, S. T.
通讯作者：
Zou, S. T.
影响因子：
29.4
作者：
Kawashima, Rei;Kawamura, Yuki I.;Dohi, Taeko
通讯作者：
Dohi, Taeko