The role of IL-6 in pathogenesis of abdominal aortic aneurysm in mice.
The role of IL-6 in pathogenesis of abdominal aortic aneurysm in mice.
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DOI：
10.1371/journal.pone.0185923
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Fukumoto Y
中科院分区：
文献类型：
--
作者：
Nishihara M;Aoki H;Ohno S;Furusho A;Hirakata S;Nishida N;Ito S;Hayashi M;Imaizumi T;Fukumoto Y
尽管腹主动脉瘤(AAA)的发病机制尚不清楚，但越来越多的证据支持炎症起着中心作用。炎症反应由多种可溶性细胞因子协调，其中IL-6是主要的促炎细胞因子之一。在这项研究中，我们研究了IL-6在小鼠腹主动脉周围暴露于CaCl2诱导的实验性AAA发病机制中的作用。我们现在报告，给予MR16-1，一种针对小鼠IL-6受体的中和性单抗，轻度抑制了AAA的发展。MR16-1引起的IL-6信号的抑制也导致STAT3活性的抑制。相反，NFJNKB活性、κ活性及基质金属蛋白酶-2和-9的表达均未见明显变化。转录组分析显示，MR16-1敏感基因编码趋化因子及其受体，以及调节血管通透性和细胞迁移的因子。然后，成像细胞仪分析一致地显示，MR16-1治疗的AAA细胞浸润减少。这些结果表明，IL-6在AAA的发病机制中起着重要但有限的作用，主要调节细胞的迁移和侵袭。这些数据还表明，IL-6活性可能在持续细胞渗透的情况下发挥重要作用，可能包括人AAA。
Although the pathogenesis of abdominal aortic aneurysm (AAA) remains unclear, evidence is accumulating to support a central role for inflammation. Inflammatory responses are coordinated by various soluble cytokines of which IL-6 is one of the major proinflammatory cytokines. In this study we examined the role of IL-6 in the pathogenesis of experimental AAA induced by a periaortic exposure to CaCl2 in mice. We now report that the administration of MR16-1, a neutralizing monoclonal antibody specific for the mouse IL-6 receptor, mildly suppressed the development of AAA. The inhibition of IL-6 signaling provoked by MR16-1 also resulted in a suppression of Stat3 activity. Conversely, no significant changes in either NFκB activity, Jnk activity or the expression of matrix metalloproteinases (Mmp) -2 and -9 were identified. Transcriptome analyses revealed that MR16-1-sensitive genes encode chemokines and their receptors, as well as factors that regulate vascular permeability and cell migration. Imaging cytometric analyses then consistently demonstrated reduced cellular infiltration for MR16-1-treated AAA. These results suggest that IL-6 plays an important but limited role in AAA pathogenesis, and primarily regulates cell migration and infiltration. These data would also suggest that IL-6 activity may play an important role in scenarios of continuous cellular infiltration, possibly including human AAA.
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影响因子：
4.6
作者：
Kimura T;Shiraishi K;Furusho A;Ito S;Hirakata S;Nishida N;Yoshimura K;Imanaka-Yoshida K;Yoshida T;Ikeda Y;Miyamoto T;Ueno T;Hamano K;Hiroe M;Aonuma K;Matsuzaki M;Imaizumi T;Aoki H
通讯作者：
Aoki H
DOI：
10.1161/atvbaha.112.300432
发表时间：
2013-02
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Johnston WF;Salmon M;Su G;Lu G;Stone ML;Zhao Y;Owens GK;Upchurch GR Jr;Ailawadi G
通讯作者：
Ailawadi G
影响因子：
15.9
作者：
Longo, GM;Xiong, WF;Baxter, BT
通讯作者：
Baxter, BT
影响因子：
4.6
作者：
Arnaoutoglou E;Kouvelos G;Koutsoumpelis A;Patelis N;Lazaris A;Matsagkas M
通讯作者：
Matsagkas M
影响因子：
39.3
作者：
Harrison SC;Smith AJ;Jones GT;Swerdlow DI;Rampuri R;Bown MJ;Aneurysm Consortium;Folkersen L;Baas AF;de Borst GJ;Blankensteijn JD;Price JF;van der Graaf Y;McLachlan S;Agu O;Hofman A;Uitterlinden AG;Franco-Cereceda A;Ruigrok YM;van't Hof FN;Powell JT;van Rij AM;Casas JP;Eriksson P;Holmes MV;Asselbergs FW;Hingorani AD;Humphries SE
通讯作者：
Humphries SE