IL-17A potentiates TNFα-induced secretion from human endothelial cells and alters barrier functions controlling neutrophils rights of passage.
IL-17A potentiates TNFα-induced secretion from human endothelial cells and alters barrier functions controlling neutrophils rights of passage.
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DOI：
10.1007/s00424-013-1354-5
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发表时间：
2014-05
影响因子：
4.5
通讯作者：
Dissing, Steen
中科院分区：
文献类型：
--
作者：
Bosteen, Markus H.;Tritsaris, Katerina;Hansen, Anker J.;Dissing, Steen
白细胞介素17A(IL-17A)是一种重要的促炎细胞因子，调节白细胞的动员和募集。为了更好地了解IL-17A如何控制白细胞在外周血液循环中通过毛细血管的运输，我们使用原代人真皮微血管内皮细胞来研究它们在IL-17A和肿瘤坏死因子α激活时的分泌潜力和屏障功能。由肿瘤坏死因子α和IL-17A激活导致p38和IκBα的磷酸化，从而使核因子κB随后被磷酸化，这一机制启动了黏附分子如E-选择素的转录。在IL-17A刺激下，中性粒细胞特异的Gro家族趋化因子在mRNA和蛋白水平上显著上调，而所有检测的非中性粒细胞特异的趋化因子在比较中保持不变。IL-17A与肿瘤坏死因子α联合应用对粒细胞集落刺激因子的诱导有明显的协同作用，且IL-17A能显著提高肿瘤坏死因子α诱导的E-选择素和ICAM-1水平。与此相一致，在体外黏附实验中，IL-17A能显著增加肿瘤坏死因子α诱导的中性粒细胞与HDMEC单层的黏附。使用以HDMEC单层为屏障的跨孔迁移试验，我们在这里表明，与单独使用肿瘤坏死因子α或IL-17A相比，预先用肿瘤坏死因子α和IL-17A预刺激内皮细胞可以提高中性粒细胞的迁移速度。这些结果表明，IL-17A和肿瘤坏死因子α协同作用，促进中性粒细胞跨越内皮细胞屏障迁移。此外，IL-17A和肿瘤坏死因子α的协同作用对于动员中性粒细胞从骨髓进入血流似乎是很重要的。
Interleukin-17A (IL-17A) is an important pro-inflammatory cytokine that regulates leukocyte mobilization and recruitment. To better understand how IL-17A controls leukocyte trafficking across capillaries in the peripheral blood circulation, we used primary human dermal microvascular endothelial cells (HDMEC) to investigate their secretory potential and barrier function when activated with IL-17A and TNFα. Activation by TNFα and IL-17A causes phosphorylation of p38 as well as IκBα whereby NFκB subsequently becomes phosphorylated, a mechanism that initiates transcription of adhesion molecules such as E-selectin. Members of the neutrophil-specific GRO-family chemokines were significantly up-regulated upon IL-17A stimulation on the mRNA and protein level, whereas all tested non-neutrophil-specific chemokines remained unchanged in comparison. Moreover, a striking synergistic effect in the induction of granulocyte colony-stimulating factors (G-CSF) was elicited when IL-17A was used in combination with TNFα, and IL-17A was able to significantly augment the levels of TNFα-induced E-selectin and ICAM-1. In accordance with this observation, IL-17A was able to markedly increase TNFα-induced neutrophil adherence to HDMEC monolayers in an in vitro adhesion assay. Using a trans-well migration assay with an HDMEC monolayer as a barrier, we here show that pre-stimulating the endothelial cells with TNFα and IL-17A together enhances the rate of neutrophil transmigration compared to TNFα or IL-17A alone. These results show that IL-17A and TNFα act in cooperation to facilitate neutrophil migration across the endothelial cell barrier. In addition, the synergistic actions of IL-17A with TNFα to secrete G-CSF appear to be important for mobilizing neutrophils from the bone marrow to the blood stream.
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DOI：
10.1084/jem.20101545
发表时间：
2010-12-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Liu Z;Miner JJ;Yago T;Yao L;Lupu F;Xia L;McEver RP
通讯作者：
McEver RP
影响因子：
4.4
作者：
Lee, Jimmy W.;Wang, Ping;Straus, Daniel S.
通讯作者：
Straus, Daniel S.
影响因子：
4.8
作者：
Hirata, Tetsuya;Osuga, Yutaka;Taketani, Yuji
通讯作者：
Taketani, Yuji
影响因子：
4.8
作者：
Guichard, C;Pedruzzi, E;Elbim, C
通讯作者：
Elbim, C
DOI：
10.1016/0006-291x(90)91400-m
发表时间：
1990-08-31
影响因子：
3.1
作者：
BENJAMIN, C;DOUGAS, I;LOBB, R
通讯作者：
LOBB, R