Suppressing Syndecan-1 Shedding Ameliorates Intestinal Epithelial Inflammation through Inhibiting NF-κB Pathway and TNF-α.

Suppressing Syndecan-1 Shedding Ameliorates Intestinal Epithelial Inflammation through Inhibiting NF-κB Pathway and TNF-α.
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通过抑制 NF-kappa B 通路和 TNF-α 抑制 Syndecan-1 脱落可改善肠上皮炎症

DOI:
10.1155/2016/6421351
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发表时间:
2016
影响因子:
2
通讯作者:
Chen Y
Chen Y
中科院分区:
医学4区
文献类型:
--
作者:
Zhang Y;Wang Z;Liu J;Zhang Z;Chen Y

文献摘要

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Syndecan-1 (SDC1), with a long variable ectodomain carrying heparan sulfate chains, participates in many steps of inflammatory responses. But reports about the efforts of SDC1's unshedding ectodomain on intestinal epithelial inflammation and the precise underlying mechanism are limited. In our study, unshedding SDC1 from intestinal epithelial cell models was established by transfecting with unshedding SDC1 plasmid into the cell, respectively. And the role of unshedding SDC1 in intestinal inflammation was further investigated. We found that components of NF-κB pathway, including P65 and IκBα, and secretion of TNF-α were upregulated upon LPS stimulation in intestinal epithelial cells. SDC1, especially through its unshed ectodomain, significantly lessened the upregulation extent. It also functioned in inhibiting migration of neutrophils by downregulating secretion of CXCL-1. Taken together, we conclude that suppressing SDC1 shedding from intestinal epithelial cells relieves severity of intestinal inflammation by inactivating NF-κB pathway and downregulating TNF-α expression. These results indicate that the ectodomain of SDC1 might be the optional therapy for intestinal inflammation.