Isogladine maleate regulates gap junctional intercellular communication-dependent epithelial barrier in human nasal epithelial cells.
Isogladine maleate regulates gap junctional intercellular communication-dependent epithelial barrier in human nasal epithelial cells.
复制标题
马来酸异糖拉定调节人鼻上皮细胞中间隙连接细胞间通讯依赖性上皮屏障。
DOI：
10.1007/s00232-015-9774-0
复制
发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Kojima T.
中科院分区：
文献类型：
--
作者：
Miyata R;Nomura K;Kakuki T;Takano K;Kohno T;Konno T;Sawada N;Himi T;Kojima T.
人鼻粘膜的气道上皮细胞作为第一个物理屏障，保护免受吸入物质和病原体的侵害。马来酸伊索拉定（IM）是一种通过上调间隙连接细胞间通讯（GJIC）增强胃粘膜保护因子的药物。GJIC被认为参与功能性紧密连接的形成。然而，IM对GJIC和人鼻上皮细胞（HNECs）上皮屏障的影响仍然未知。为了研究IM对HNECs中GJIC和紧密连接屏障的影响，用IM和GJIC抑制剂oleamide和18β-GA处理转染人端粒酶逆转录酶（hTERT-HNECs）的HNECs的原代培养物。在用TLR 3配体poly（I：C）处理之前，用IM预处理一些细胞，以检查IM是否通过TLR 3介导的信号通路阻止变化。在hTERT-HNECs中，GJIC阻断剂减少紧密连接分子claudin-1、claudin-4、claudin-7、occludin、tricellulin和JAM-A的表达。IM诱导GJIC活性，并在蛋白和mRNA水平上增强claudin-1、-4和JAM-A的表达，增强屏障功能。GJIC阻断剂可阻止IM诱导的紧密连接蛋白的增加。IM可抑制poly（I：C）诱导的JAM-A的减少，但不能抑制poly（I：C）诱导的IL-8和TNF-α的产生。结论：IM可通过调节GJIC维持上气道鼻上皮GJIC依赖的紧密连接屏障。因此，IM可能用作鼻喷雾剂，以防止由病毒感染和暴露于人鼻粘膜中的过敏原引起的上皮屏障破坏。
The airway epithelium of the human nasal mucosa acts as the first physical barrier that protects against inhaled substances and pathogens. Irsogladine maleate (IM) is an enhancer of gastric mucosal protective factors via upregulation of gap junctional intercellular communication (GJIC). GJIC is thought to participate in the formation of functional tight junctions. However, the effects of IM on GJIC and the epithelial barrier in human nasal epithelial cells (HNECs) remain unknown. To investigate the effects of IM on GJIC and the tight junctional barrier in HNECs, primary cultures of HNECs transfected with human telomerase reverse transcriptase (hTERT-HNECs) were treated with IM and the GJIC inhibitors oleamide and 18β-GA. Some cells were pretreated with IM before treatment with TLR3 ligand poly(I:C) to examine whether IM prevented the changes via TLR3-mediated signal pathways. In hTERT-HNECs, GJIC blockers reduced the expression of tight junction molecules claudin-1, -4, -7, occludin, tricellulin, and JAM-A. IM induced GJIC activity and enhanced the expression of claudin-1, -4, and JAM-A at the protein and mRNA levels with an increase of barrier function. GJIC blockers prevented the increase of the tight junction proteins induced by IM. Furthermore, IM prevented the reduction of JAM-A but not induction of IL-8 and TNF-α induced by poly(I:C). In conclusion, IM can maintain the GJIC-dependent tight junctional barrier via regulation of GJIC in upper airway nasal epithelium. Therefore, it is possible that IM may be useful as a nasal spray to prevent the disruption of the epithelial barrier by viral infections and exposure to allergens in human nasal mucosa.