Expression of the C-C chemokine MIP-3α/CCL20 in human epidermis with impaired permeability barrier function

Expression of the C-C chemokine MIP-3α/CCL20 in human epidermis with impaired permeability barrier function
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DOI:
10.1034/j.1600-0625.2002.110205.x
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发表时间:
2002-04-01
影响因子:
3.6
通讯作者:
Heufler, C
Heufler, C
中科院分区:
医学2区
文献类型:
--
作者:
Schmuth, M;Neyer, S;Heufler, C

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对皮肤的外部攻击之后是表皮反应,包括DNA、脂质、细胞因子的合成和抗原呈递细胞的迁移。MIP-3 α(CCL 20,LARC,Exodus-1,Scya 20)是最近描述的C-C趋化因子,主要在淋巴外组织中表达,已知其引导树突状细胞前体和记忆淋巴细胞迁移至抗原侵袭位点。我们评估了MIP-3a在人类皮肤中的表达,采用半定量聚合酶链反应。在体内,MIP-3 α mRNA在未处理的人表皮中以低水平组成型表达。急性破坏表皮通透性屏障后,MIP-3 α mRNA在表皮部分中上调,而真皮MIP-3 α mRNA水平保持不变。在体外,MIP-3 α在用IL-1 α和TNF-α处理的培养角质形成细胞中增加,并且存在于未成熟和成熟树突状细胞、THP-1单核细胞和活化T细胞中。最后,银屑病、接触性皮炎和蕈样肉芽肿患者的皮肤活检显示出丰富的表达。在特应性皮炎和移植物抗宿主病的活检中,存在弱信号,而在硬皮病和中毒性表皮坏死松解症中未发现表达。我们的结论是MIP-3 α mRNA的调节是表皮对外部攻击的反应的一部分。它的上调可能是一个危险的信号,增加免疫监视屏障破坏皮肤和炎症性皮肤疾病与受损的屏障功能,以抵消潜在的抗原入侵。
External assault to the skin is followed by an epidermal response including synthesis of DNA, lipids, cytokines and migration of antigen presenting cells. MIP-3alpha (CCL20, LARC, Exodus-1, Scya20) is a recently described C-C chemokine, predominantly expressed in extralymphoid tissue, which is known to direct migration of dendritic cell precursors and memory lymphocytes to sites of antigen invasion. We assessed the expression of MIP-3a in human skin using semi-quantitative polymerase chain reaction. In vivo, MIP-3alpha mRNA was constitutively expressed at low levels in untreated human epidermis. After acute disruption of the epidermal permeabiltiy barrier MIP-3alpha mRNA was upregulated in the epidermal fraction, whereas dermal MIP-3alpha mRNA levels remained unchanged. In vitro, MIP-3alpha was increased in cultured keratinocytes treated with IL- 1alpha and TNF-alpha and was present in immature and mature dendritic cells, THP-1 monocytic cells and activated T cells. Finally, skin biopsies from patients with psoriasis, contact dermatitis and mycosis fungoides showed abundant expression. In biopsies from atopic dermatitis and graft vs. host disease a weak signal was present, whereas no expression was found in scleroderma and toxic epidermal necrolysis. We conclude that regulation of MIP-3alpha mRNA is part of the epidermal response to external assault. Its upregulation may represent a danger signal for increased inummosurveillance in barrier disrupted skin and inflammatory skin conditions with impaired barrier function to counteract potential antigen invasion.