Norepinephrine and adenosine-5'-triphosphate synergize in inducing IL-6 production by human dermal microvascular endothelial cells.
Norepinephrine and adenosine-5'-triphosphate synergize in inducing IL-6 production by human dermal microvascular endothelial cells.
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DOI：
10.1016/j.cyto.2013.08.005
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发表时间：
2013-11
期刊：
影响因子：
3.8
通讯作者：
Granstein, Richard D.
中科院分区：
文献类型：
--
作者：
Stohl, Lori L.;Zang, Julie B.;Ding, Wanhong;Manni, Michela;Zhou, Xi K.;Granstein, Richard D.
内皮细胞（EC）在皮肤炎症中起重要作用，部分是通过释放炎性趋化因子/细胞因子。由于真皮血管受交感神经支配，交感神经递质去甲肾上腺素（NE）和共递质腺苷-5 '-三磷酸（ATP）可调节EC炎性因子的表达。我们专注于IL-6的调节，因为它具有许多炎症和免疫功能，包括参与Th 17细胞分化。引人注目的是，NE和ATP协同诱导人真皮微血管内皮细胞系（HMEC-1）释放IL-6。肾上腺素能拮抗剂和激动剂研究表明，NE对IL-6释放的影响主要是通过β2-肾上腺素能受体（AR）介导的。通过实时PCR，IL-6 mRNA也在HMEC-1细胞中协同诱导。NE和ATP的这种协同作用在原代人真皮内皮细胞（pHDMECs）中再现，并且也主要由β2-AR介导。在应激条件下，交感神经系统的激活可导致真皮血管周围的交感神经释放ATP和NE，并诱导EC产生IL-6。然后IL-6可以参与免疫和炎症过程，包括Th 17细胞的产生。以这种方式产生IL-6可能解释银屑病的应激诱导的恶化，以及可能解释涉及Th 17型免疫的其他皮肤疾病。
Endothelial cells (ECs) play important roles in cutaneous inflammation, in part, by release of inflammatory chemokines/cytokines. Because dermal blood vessels are innervated by sympathetic nerves, the sympathetic neurotransmitter norepinephrine (NE) and the co-transmitter adenosine-5’-triphosphate (ATP) may regulate expression of EC inflammatory factors. We focused on IL-6 regulation because it has many inflammatory and immune functions, including participation in Th17 cell differentiation. Strikingly, NE and ATP synergistically induced release of IL-6 by a human dermal microvascular endothelial cell line (HMEC-1). Adrenergic antagonist and agonist studies indicated that the effect of NE on induced IL-6 release is primarily mediated by β2-adrenergic receptors (ARs). By real-time PCR IL-6 mRNA was also synergistically induced in HMEC-1 cells. This synergistic effect of NE and ATP was reproduced in primary human dermal endothelial cells (pHDMECs) and is also primarily mediated by β2-ARs. Under conditions of stress, activation of the symphathetic nervous system may lead to release of ATP and NE by sympathetic nerves surrounding dermal blood vessels with induction of IL-6 production by ECs. IL-6 may then participate in immune and inflammatory processes including generation of Th17 cells. Production of IL-6 in this manner might explain stress-induced exacerbation of psoriasis, and perhaps, other skin disorders involving Th17-type immunity.
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DOI：
10.3410/b1-46
发表时间：
2009-06-09
期刊：
F1000 biology reports
影响因子：
--
作者：
Burnstock G
通讯作者：
Burnstock G
DOI：
10.1186/1710-1492-4-1-2
发表时间：
2008-03-15
期刊：
Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology
影响因子：
--
作者：
Dhabhar FS
通讯作者：
Dhabhar FS
影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
4.6
作者：
Boniface, K.;Guignouard, E.;Morel, F.
通讯作者：
Morel, F.
影响因子：
6.5
作者：
ADES, EW;CANDAL, FJ;LAWLEY, TJ
通讯作者：
LAWLEY, TJ