Leukoregulin induction of protein expression in human orbital fibroblasts: evidence for anatomical site-restricted cytokine-target cell interactions.
Leukoregulin induction of protein expression in human orbital fibroblasts: evidence for anatomical site-restricted cytokine-target cell interactions.
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DOI：
10.1073/pnas.95.15.8904
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发表时间：
1998-07
影响因子：
11.1
通讯作者：
Donald A. Young;Charles H. Evans;Terry J. Smith
中科院分区：
文献类型：
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作者：
Donald A. Young;Charles H. Evans;Terry J. Smith
在甲状腺相关眼病中观察到的眼眶结缔组织中的严重炎症反应和透明质酸蓄积的分子基础尚不清楚。此外，Graves病的眼眶表现与胫前皮肤表现（局限性皮肤病）之间的联系尚未确定。我们最近报道，leukoregulin，活化的T淋巴细胞衍生的细胞因子，显着诱导透明质酸的合成和人眼眶成纤维细胞培养中的胰高血糖素-内过氧化物H合酶2。在目前的研究中，利用巨大的二维凝胶电泳，我们发现，眼眶成纤维细胞组成型表达的蛋白质谱，区分他们从腹壁和pretibium皮肤成纤维细胞。我们进一步证明，leukoregulin，当存在于培养基中16小时，上调一组眼眶成纤维细胞蛋白不存在于未经处理的培养物或成纤维细胞从腹壁。然而，胫骨前成纤维细胞中存在一些相同的蛋白诱导。这些白细胞调节素诱导的蛋白质表达变化被地塞米松（10 nM）完全阻断。我们的研究结果是第一个确定蛋白质，似乎是表达和差异调节的解剖部位限制的方式在眼眶和胫骨前成纤维细胞，似乎建立了成纤维细胞之间的分子联系，从眼眶和胫骨前皮肤。
The molecular basis for the profound inflammatory response and the accumulation of hyaluronan in orbital connective tissues seen in thyroid-associated ophthalmopathy is unknown. Moreover, the link between the orbital manifestations of Graves' disease and those in the pretibial skin, localized dermopathy, has yet to be established. We have reported recently that leukoregulin, an activated T lymphocyte-derived cytokine, dramatically induces hyaluronan synthesis and prostaglandin-endoperoxide H synthase 2 in human orbital fibroblasts in culture. In the current studies, utilizing giant two-dimensional gel electrophoresis, we find that orbital fibroblasts express constitutively a protein profile that distinguishes them from skin fibroblasts derived from the abdominal wall and from the pretibium. We further demonstrate that leukoregulin, when present in culture medium for 16 hr, up-regulates a set of orbital fibroblast proteins not present in untreated cultures or in fibroblasts from the abdominal wall. However, some of the same protein inductions are present in the pretibial fibroblasts. These leukoregulin-induced changes in protein expression are completely blocked by dexamethasone (10 nM). Our findings are the first to identify proteins that appear to be expressed and differentially regulated in an anatomical site-restricted manner in orbital and pretibial fibroblasts and seem to establish a molecular link between fibroblasts from the orbit and those in pretibial skin.