Orbital fibroblasts from patients with thyroid-associated ophthalmopathy overexpress CD40: CD154 hyperinduces IL-6, IL-8, and MCP-1.
Orbital fibroblasts from patients with thyroid-associated ophthalmopathy overexpress CD40: CD154 hyperinduces IL-6, IL-8, and MCP-1.
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DOI：
10.1167/iovs.08-2328
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发表时间：
2009-05
影响因子：
4.4
通讯作者：
Douglas RS
中科院分区：
文献类型：
--
作者：
Hwang CJ;Afifiyan N;Sand D;Naik V;Said J;Pollock SJ;Chen B;Phipps RP;Goldberg RA;Smith TJ;Douglas RS
成纤维细胞多样性代表了一个新兴的概念，对我们理解组织炎症、修复和重塑至关重要。眼眶成纤维细胞异质地显示Thy-1，并表现出独特的表型属性，这可能解释了人类眼眶对甲状腺相关眼病（TAO）的易感性。在本研究中，我们研究了CD40连接对TAO患者成纤维细胞中巨噬细胞化学引诱蛋白-1 （MCP-1）、IL-6和IL-8表达的作用。经知情同意，从TAO患者和接受其他非炎症性手术的患者获得的组织中培养人眼眶成纤维细胞。然后用流式细胞术、显微镜和细胞因子检测成纤维细胞。我们报道TAO患者的眼眶成纤维细胞表达CD40水平升高。表面CD40可被干扰素进一步上调。γ (IFN-γ)在TAO和对照成纤维细胞中的表达。这种上调是通过Jak2介导的，可以被地塞米松和AG490阻断，AG490是一种强效和特异性的酪氨酸激酶抑制剂。CD40的配体CD154在TAO成纤维细胞中上调IL-6、IL-8和MCP-1的表达，但在对照培养中没有上调。Thy-1+成纤维细胞比Thy-1 -成纤维细胞表现出更高的CD40水平，并在很大程度上负责这种细胞因子的产生。IL-1β在tao来源的成纤维细胞中也更强烈地诱导MCP-1、IL-6和IL-8。眼眶成纤维细胞的特征及其细胞因子和受体的差异表达对于理解TAO的部位特异性和开发特异性治疗方法是非常宝贵的。
Fibroblast diversity represents an emerging concept critical to our understanding of tissue inflammation, repair and remodeling. Orbital fibroblasts heterogeneously display Thy-1 and exhibit unique phenotypic attributes that may explain the susceptibility of the human orbit to thyroid-associated ophthalmopathy (TAO). In the current study we investigate the role of CD40 ligation upon macrophage chemoattractant protein -1 (MCP-1), IL-6 and IL-8 expression in fibroblasts from patients with TAO. Human orbital fibroblasts were cultured from tissues obtained with informed consent from patients with TAO and from patients undergoing surgery for other, non-inflammatory conditions. The fibroblasts were then examined by flow cytometry, microscopy, and cytokine assays. We report that orbital fibroblasts from patients with TAO express elevated levels of CD40. Surface CD40 can be further up-regulated by interferon.γ (IFN-γ) in both TAO and control fibroblasts. This up-regulation is mediated through Jak2 and can be blocked by dexamethasone and AG490, a powerful and specific inhibitor of the tyrosine kinase. Treatment with CD154, the ligand for CD40, up-regulates the expression of IL-6, IL-8 and MCP-1 in TAO fibroblasts, but fails to do so in control cultures. Thy-1+ fibroblasts displayed higher CD40 levels than do their Thy-1− counterparts and are largely responsible for this cytokine production. IL-1β also induces MCP-1, IL-6 and IL-8 more vigorously in TAO-derived fibroblasts. Characterization of orbital fibroblasts and their differential expression of cytokines and receptors should prove invaluable in understanding the site-specific nature of TAO and the development of specific therapies.
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影响因子：
4.8
作者：
Chen, Beiling;Tsui, Shanli;Smith, Terry J.
通讯作者：
Smith, Terry J.
影响因子：
3.6
作者：
Diehl, S;Rincón, M
通讯作者：
Rincón, M
影响因子：
4.1
作者：
Burnstine, MA;Elner, SG;Elner, VM
通讯作者：
Elner, VM
DOI：
10.1097/00002341-199803000-00008
发表时间：
1998-03-01
影响因子：
2
作者：
Elner, VM;Burnstine, MA;Elner, SG
通讯作者：
Elner, SG
影响因子：
4.4
作者：
Han, Rui;Chen, Beiling;Smith, Terry J.
通讯作者：
Smith, Terry J.