IL-17 and TNF-α sustain neutrophil recruitment during inflammation through synergistic effects on endothelial activation.
IL-17 and TNF-α sustain neutrophil recruitment during inflammation through synergistic effects on endothelial activation.
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DOI：
10.4049/jimmunol.1200385
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发表时间：
2012-06-15
期刊：
影响因子：
--
通讯作者：
Lichtman AH
中科院分区：
文献类型：
--
作者：
Griffin GK;Newton G;Tarrio ML;Bu DX;Maganto-Garcia E;Azcutia V;Alcaide P;Grabie N;Luscinskas FW;Croce KJ;Lichtman AH
白细胞介素17 A（IL-17）是由TH 17细胞产生的标志性细胞因子，并且已经涉及宿主对感染的防御以及自身免疫和心血管疾病的病理生理学。然而，关于IL-17对内皮活化和白细胞流入炎症部位的影响知之甚少。我们假设，与TH 1细胞因子IFNγ相比，IL-17将诱导一种独特的内皮激活和白细胞募集模式。我们发现，IL-17单独对培养的内皮细胞具有最小的激活作用，而TNFα和IL-17的组合产生了P-选择素和E-选择素表达的协同增加。使用小鼠提睾肌活体显微镜，我们发现TNFα和IL-17也导致体内微血管内皮上E-选择素依赖性白细胞滚动的协同增加。此外，TNFα和IL-17增强了内皮细胞嗜酸性趋化因子CXCL 1、CXCL 2和CXCL 5的表达，并导致体内白细胞迁移和CXCR 2依赖性中性粒细胞功能性增加，但在平行板流动室系统中不导致T细胞迁移。相比之下，TNFα和IFNγ激活内皮细胞优先诱导整合素配体ICAM 1和VCAM 1以及T细胞趋化因子CXCL 9、CXCL 10和CCL 5的表达。这些作用进一步与层流剪切流下T细胞而非中性粒细胞迁移的功能性增加相关。总体而言，这些数据表明IL-17和TNFα以协同方式诱导不同的内皮活化模式，维持并增强中性粒细胞流入炎症部位。
Interleukin 17A (IL-17) is the signature cytokine produced by TH17 cells and has been implicated in host defense against infection and the pathophysiology of autoimmunity and cardiovascular disease. Little is known, however, about the influence of IL-17 on endothelial activation and leukocyte influx to sites of inflammation. We hypothesized that IL-17 would induce a distinct pattern of endothelial activation and leukocyte recruitment when compared to the TH1 cytokine, IFNγ. We found that IL-17 alone had minimal activating effects on cultured endothelium, while the combination of TNFα and IL-17 produced a synergistic increase in the expression of both P-selectin and E-selectin. Using intravital microscopy of the mouse cremaster muscle, we found that TNFα and IL-17 also led to a synergistic increase in E-selectin dependent leukocyte rolling on microvascular endothelium in vivo. In addition, TNFα and IL-17 enhanced endothelial expression of the neutrophilic chemokines CXCL1, CXCL2, and CXCL5, and led to a functional increase in leukocyte transmigration in vivo and CXCR2-dependent neutrophil but not T-cell transmigration in a parallel-plate flow chamber system. By contrast, endothelial activation with TNFα and IFNγ preferentially induced the expression of the integrin-ligands ICAM1 and VCAM1, as well as the T-cell chemokines CXCL9, CXCL10, and CCL5. These effects were further associated with a functional increase in T-cell but not neutrophil transmigration under laminar shear flow. Overall, these data show that IL-17 and TNFα act in a synergistic manner to induce a distinct pattern of endothelial activation that sustains and enhances neutrophil influx to sites of inflammation.
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Th1和Th17淋巴细胞粘附于内皮的差异。
DOI：
10.4049/jimmunol.1101647
发表时间：
2012-02-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Alcaide P;Maganto-Garcia E;Newton G;Travers R;Croce KJ;Bu DX;Luscinskas FW;Lichtman AH
通讯作者：
Lichtman AH
影响因子：
25.7
作者：
Khandoga, Andrej;Huettinger, Stefanie;Krombach, Fritz
通讯作者：
Krombach, Fritz
影响因子：
4.4
作者：
Erbel, Christian;Chen, Lili;Dengler, Thomas J.
通讯作者：
Dengler, Thomas J.
影响因子：
15.9
作者：
Jung, U;Norman, KE;Ley, K
通讯作者：
Ley, K
影响因子：
6.4
作者：
Huang, WT;Na, L;Schwarzenberger, P
通讯作者：
Schwarzenberger, P