The transcriptomic response of rat hepatic stellate cells to endotoxin: implications for hepatic inflammation and immune regulation.
The transcriptomic response of rat hepatic stellate cells to endotoxin: implications for hepatic inflammation and immune regulation.
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大鼠肝星状细胞对内毒素的转录组反应：对肝炎和免疫调节的影响。
DOI：
10.1371/journal.pone.0082159
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Gandhi CR
中科院分区：
文献类型：
--
作者：
Harvey SA;Dangi A;Tandon A;Gandhi CR
肝星状细胞（hepatic stellate cells，HSC）位于Disse窦周隙，通过物理结合（细胞体和胞质过程通过内皮细胞穿孔进入窦状隙）和产生多种细胞因子和趋化因子与所有肝细胞类型进行通讯。细菌脂多糖（LPS），其循环水平在肝脏疾病和移植中升高，刺激HSC产生增加量的细胞因子和趋化因子。尽管最近的研究为HSC在肝脏炎症和免疫调节中的作用提供了强有力的证据，但HSC精心制作的炎症和免疫调节分子的数量可能比目前已知的要多得多。在这里，我们报告了LPS刺激的大鼠HSC中炎症和免疫调节分子的基因表达谱的时间依赖性变化，以及它们通过生化分析的验证。LPS强烈上调LPS反应元件（TLR2和TLR7），但不影响TLR4和下调TLR9。LPS还上调MAPK、NFκB、STAT、SOCS、IRAK和干扰素信号通路中的基因，以及多种CC和CXC趋化因子和IL 17 F。有趣的是，LPS以限制其活化和纤维化活性的方式调节与TGFβ和HSC活化相关的基因。这些数据表明，LPS刺激的HSC通过改变许多相关基因的表达而成为调节肝脏炎症和免疫反应的主要细胞类型，从而在包括肝脏疾病和移植在内的肝脏病理生理学中发挥突出作用。
With their location in the perisinusoidal space of Disse, hepatic stellate cells (HSCs) communicate with all of the liver cell types both by physical association (cell body as well as cytosolic processes penetrating into sinusoids through the endothelial fenestrations) and by producing several cytokines and chemokines. Bacterial lipopolysaccharide (LPS), circulating levels of which are elevated in liver diseases and transplantation, stimulates HSCs to produce increased amounts of cytokines and chemokines. Although recent research provides strong evidence for the role of HSCs in hepatic inflammation and immune regulation, the number of HSC-elaborated inflammatory and immune regulatory molecules may be much greater then known at the present time. Here we report time-dependent changes in the gene expression profile of inflammatory and immune-regulatory molecules in LPS-stimulated rat HSCs, and their validation by biochemical analyses. LPS strongly up-regulated LPS-response elements (TLR2 and TLR7) but did not affect TLR4 and down-regulated TLR9. LPS also up-regulated genes in the MAPK, NFκB, STAT, SOCS, IRAK and interferon signaling pathways, numerous CC and CXC chemokines and IL17F. Interestingly, LPS modulated genes related to TGFβ and HSC activation in a manner that would limit their activation and fibrogenic activity. The data indicate that LPS-stimulated HSCs become a major cell type in regulating hepatic inflammatory and immunological responses by altering expression of numerous relevant genes, and thus play a prominent role in hepatic pathophysiology including liver diseases and transplantation.
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DOI：
10.1073/pnas.95.23.13812
发表时间：
1998-11-10
影响因子：
11.1
作者：
Belz, GT;Altman, JD;Doherty, PC
通讯作者：
Doherty, PC
影响因子：
3.1
作者：
Dhupar, Rajeev;Klune, John R.;Tsung, Allan
通讯作者：
Tsung, Allan
影响因子：
4.8
作者：
Fitzner, Brit;Brock, Peter;Jaster, Robert
通讯作者：
Jaster, Robert
DOI：
10.1042/bj20080925
发表时间：
2009-01-15
期刊：
The Biochemical journal
影响因子：
--
作者：
Cismasiu VB;Duque J;Paskaleva E;Califano D;Ghanta S;Young HA;Avram D
通讯作者：
Avram D
影响因子：
120.7
作者：
Feng, Sandy;Ekong, Udeme D.;Tchao, Nadia K.
通讯作者：
Tchao, Nadia K.