Macrophage migration inhibitory factor is critical for dengue NS1-induced endothelial glycocalyx degradation and hyperpermeability.
Macrophage migration inhibitory factor is critical for dengue NS1-induced endothelial glycocalyx degradation and hyperpermeability.
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DOI：
10.1371/journal.ppat.1007033
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发表时间：
2018-04
期刊：
影响因子：
6.7
通讯作者：
Yeh TM
中科院分区：
文献类型：
--
作者：
Chen HR;Chao CH;Liu CC;Ho TS;Tsai HP;Perng GC;Lin YS;Wang JR;Yeh TM
Vascular leakage is one of the salient characteristics of severe dengue. Nonstructural protein 1 (NS1) of dengue virus (DENV) can stimulate endothelial cells to secrete endothelial hyperpermeability factor, macrophage migration inhibitory factor (MIF), and the glycocalyx degradation factor heparanase 1 (HPA-1). However, it is unclear whether MIF is directly involved in NS1-induced glycocalyx degradation. In this study, we observed that among NS1, MIF and glycocalyx degradation-related molecules, the HPA-1, metalloproteinase 9 (MMP-9) and syndecan 1 (CD138) serum levels were all increased in dengue patients, and only NS1 and MIF showed a positive correlation with the CD138 level in severe patients. To further characterize and clarify the relationship between MIF and CD138, we used recombinant NS1 to stimulate human cells in vitro and challenge mice in vivo. Our tabulated results suggested that NS1 stimulation could induce human endothelial cells to secrete HPA-1 and immune cells to secrete MMP-9, resulting in endothelial glycocalyx degradation and hyperpermeability. Moreover, HPA-1, MMP-9, and CD138 secretion after NS1 stimulation was blocked by MIF inhibitors or antibodies both in vitro and in mice. Taken together, these results suggest that MIF directly engages in dengue NS1-induced glycocalyx degradation and that targeting MIF may represent a possible therapeutic approach for preventing dengue-induced vascular leakage. DENV NS1 induces endothelial glycocalyx degradation and hyperpermeability via HPA-1 and MMP-9 activation in an MIF-dependent manner.
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影响因子：
17.1
作者：
Beatty, P. Robert;Puerta-Guardo, Henry;Harris, Eva
通讯作者：
Harris, Eva
影响因子：
0.8
作者：
Chen, Hong-Ru;Yeh, Trai-Ming
通讯作者：
Yeh, Trai-Ming
DOI：
10.4049/jimmunol.1700029
发表时间：
2017-05-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Hertz T;Beatty PR;MacMillen Z;Killingbeck SS;Wang C;Harris E
通讯作者：
Harris E
影响因子：
3.8
作者：
Chen HR;Chuang YC;Lin YS;Liu HS;Liu CC;Perng GC;Yeh TM
通讯作者：
Yeh TM
DOI：
10.1186/s13054-015-0741-z
发表时间：
2015-01-28
期刊：
Critical care (London, England)
影响因子：
--
作者：
Chelazzi C;Villa G;Mancinelli P;De Gaudio AR;Adembri C
通讯作者：
Adembri C