Guanylate binding protein-1-mediated epithelial barrier in human salivary gland duct epithelium
Guanylate binding protein-1-mediated epithelial barrier in human salivary gland duct epithelium
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DOI：
10.1016/j.yexcr.2018.07.033
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发表时间：
2018-10-01
影响因子：
3.7
通讯作者：
Kojima, Takashi
中科院分区：
文献类型：
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作者：
Konno, Takumi;Takano, Kenichi;Kojima, Takashi
鸟苷酸结合蛋白-1（GBP-1）是一种干扰素诱导的大GT3，参与上皮细胞紧密连接处的屏障。为了研究GBP-1在上皮屏障中的作用，用促炎细胞因子IFN γ、IL-1 β、TNF α和生长因子TGF-β处理原代人唾液腺导管上皮细胞。用IFN γ、IL-1 β或TNF α治疗显著增强GBP-1和上皮屏障功能，并且不仅诱导CLDN-7，而且诱导三细胞紧密连接分子脂解刺激的脂蛋白受体（LSR）。通过siRNA敲低GBP-1可诱导紧密连接分子的内吞作用，并阻止CLDN-7和LSR的增加，以及IFN γ或TNF α治疗诱导的上皮屏障功能的上调。用PKC α抑制剂处理诱导GBP-1、CLDN-7和LSR的表达，并增强上皮屏障功能。在几乎完整的唾液腺导管与IgG 4相关的疾病（IgG 4-RD）的患者表明IgG阳性浆细胞的显著浸润，GBP-1，CLDN-7和LSR的表达增加。这些结果表明GBP-1可能在正常人唾液腺导管上皮的屏障功能中起关键作用，并在IgG 4-RD疾病的导管上皮中起预防作用。
Guanylate-binding protein-1 (GBP-1) is an interferon-inducible large GTPase involved in the epithelial barrier at tight junctions. To investigate the role of GBP-1 in the epithelial barrier, primary human salivary gland duct epithelial cells were treated with the the proinflammatory cytokines IFN gamma, IL-1 beta, TNF alpha and the growth factor TGF-beta. Treatment with IFN gamma, IL-1 beta, or TNF alpha markedly enhanced GBP-1 and the epithelial barrier function, and induced not only CLDN-7 but also the tricellular tight junction molecule lipolysis-stimulated lipoprotein receptor (LSR). Knockdown of GBP-1 by its siRNA induced endocytosis of tight junction molecules, and prevented the increases of CLDN-7 and LSR with the upregulation of the epithelial barrier function induced by treatment with IFN gamma or TNF alpha. Treatment with a PKC alpha inhibitor induced expression of GBP-1, CLDN-7 and LSR and enhanced the epithelial barrier function. In almost intact salivary gland ducts from patients with IgG4-related disease (IgG4-RD) indicated significant infiltration of IgG-positive plasma cells, expression of GBP-1, CLDN-7 and LSR was increased. These findings indicated that GBP-1 might play a crucial role in barrier function of normal human salivary gland duct epithelium and perform a preventive role in the duct epithelium of IgG4-RD disease.