Up-regulation of CC chemokine ligand 20 and its receptor CCR6 in the lesional skin of early systemic sclerosis.

Up-regulation of CC chemokine ligand 20 and its receptor CCR6 in the lesional skin of early systemic sclerosis.
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早期系统性硬化症病变皮肤中CC趋化因子配体20及其受体CCR6的上调。

DOI:
10.1684/ejd.2011.1469
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发表时间:
2011-10
影响因子:
2.5
通讯作者:
Li Lin
Li Lin
中科院分区:
医学4区
文献类型:
--
作者:
Ren Ya-li;Yang Jin;Tu Ya-ting;He Xiao-liang;Tian Fen;Tao Juan;Li Yan;Shen Guan-xin;Wang Li;Xu Guang-fen;Tan Zhi-jian;Li Lin

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单核细胞(MNC)浸润是系统性硬化症(SSc)皮肤最早的病理改变之一。然而,对这些细胞在皮肤病变中的募集知之甚少。最近,趋化因子的作用已被建议在SSc的发病机制。本文研究了CC趋化因子CCL20及其受体CCR6在早期SSc皮损中的表达和分布,以及正常皮肤成纤维细胞(NDF)和硬皮病皮肤成纤维细胞(SSDF)中CCL20表达和募集MNC能力的差异。我们发现,与正常人皮肤相比,在SSc中CCL20及其受体CCR6的表达明显上调。SSc皮损组织中mRNA表达水平显著高于正常皮肤组织。SSDF显示CCL20 mRNA和蛋白的组成性表达增加。Th1型细胞因子TNF-α和IL-1 β可显著增加NDF和SSDF中CCL 20的表达,并呈剂量和时间依赖性。SSDF上清液对PBMC的趋化活性强于NDF上清液。因此,我们的研究结果表明,CCL20释放从姜黄素激活的SSDF中起着重要的作用,通过进一步招募更多的MNCs到皮肤的SSc的诱导。
Mononuclear cell (MNC) infiltrate is one of the earliest pathological changes in systemic sclerosis (SSc) skin. However, little is known about the recruitment of these cells into skin lesions. Recently, the role of chemokines has been suggested in the pathogenesis of SSc. Here we studied the expressions and distributions of CC chemokine CCL20 and its receptor CCR6 in early SSc skin lesions and the difference in CCL20 expressions and ability to recruite MNCs of normal dermal fibroblast (NDF) and scleroderma dermal fibroblast (SSDF). We found that the expressions of CCL20 and its receptor CCR6 were obviously up-regulated in SSc in contrast to normal human skin. mRNA levels were significantly expressed in SSc lesional skins vs normal skin tissues. SSDF displayed increased constitutive expressions of CCL20 mRNA and protein. In addition, Th1 cytokines (TNF-α and IL-1β) remarkably increased the expression of CCL20 in both NDF and SSDF in a dose- and time-dependent manner. Supernatants from SSDF showed stronger chemotactic activity to PBMCs than those from NDF. Thus our findings suggest that CCL20 released from cytokine-activated SSDF plays an important role in the induction of SSc by further recruiting more MNCs to the skin.
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