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白细胞介素-19和白细胞介素-20及其受体在银屑病中的基因表达动态

The dynamics of gene expression of interleukin-19 and interleukin-20 and their receptors in psoriasis.

作者信息

Otkjaer K, Kragballe K, Funding A T, Clausen J T, Noerby P L, Steiniche T, Iversen L

机构信息

Department of Dermatology, Aarhus Hospital, P.P. Ørumsgade 11, University of Aarhus, DK-8000 Aarhus C, Denmark.

出版信息

Br J Dermatol. 2005 Nov;153(5):911-8. doi: 10.1111/j.1365-2133.2005.06800.x.

DOI:10.1111/j.1365-2133.2005.06800.x
PMID:16225599
Abstract

BACKGROUND

Interleukin (IL)-20 and IL-19 are recently discovered members of the IL-10 family of cytokines. The skin of transgenic mice overexpressing IL-20 shows histological changes resembling some of those seen in psoriasis, i.e. thickened epidermis, hyperkeratosis and a compact stratum corneum. IL-19 and IL-20, as well as their receptor complexes, IL-20Ralpha/IL-20Rbeta and IL-22Ralpha/IL-20Rbeta, are expressed in human skin.

OBJECTIVES

To study the dynamics of IL-19 and IL-20 gene expression as well as the expression of their receptor subunits in psoriatic skin lesions.

METHODS

Punch biopsies from patients with plaque-type psoriasis were collected before, during and after 28 days of treatment with either calcipotriol or ciclosporin (CsA). IL-20, IL-19, IL-20Ralpha, IL-20Rbeta and IL-22Ralpha mRNA expression were determined by quantitative reverse transcriptase-polymerase chain reaction.

RESULTS

We found IL-19 and IL-20 mRNA expression in lesional psoriatic skin to be strongly upregulated compared with nonlesional psoriatic skin by a factor of 65 and 22, respectively. In contrast to previous reports, IL-20Ralpha and IL-20Rbeta mRNA levels showed a modest but statistically significant decrease in lesional psoriatic skin compared with nonlesional psoriatic skin. During treatment with calcipotriol or CsA, IL-19 and IL-20 mRNA levels decrease in accordance with the clinical improvement of psoriasis. Neither IL-19, IL-20, nor receptor subunit mRNA expression in lesional psoriatic skin reaches the levels of nonlesional skin during this short-term treatment. These findings are in line with the residual disease activity observed at the end of treatment.

CONCLUSIONS

The increased IL-19 and IL-20 mRNA expression levels in lesional psoriatic skin suggest that these two cytokines play a role in the pathogenesis of psoriasis. An imbalance in the receptor complexes for IL-19 and IL-20 might contribute to their suspected pathogenic effects.

摘要

背景

白细胞介素(IL)-20和IL-19是最近发现的IL-10细胞因子家族成员。过表达IL-20的转基因小鼠皮肤显示出一些类似于银屑病的组织学变化,即表皮增厚、角化过度和致密的角质层。IL-19和IL-20以及它们的受体复合物IL-20Rα/IL-20Rβ和IL-22Rα/IL-20Rβ在人类皮肤中表达。

目的

研究银屑病皮损中IL-19和IL-20基因表达的动态变化及其受体亚基的表达情况。

方法

收集斑块型银屑病患者在使用卡泊三醇或环孢素(CsA)治疗前、治疗期间及治疗28天后的打孔活检组织。通过定量逆转录聚合酶链反应测定IL-20、IL-19、IL-20Rα、IL-20Rβ和IL-22Rα mRNA的表达。

结果

我们发现,与非皮损性银屑病皮肤相比,银屑病皮损皮肤中IL-19和IL-20 mRNA的表达分别强烈上调65倍和22倍。与先前的报道相反,与非皮损性银屑病皮肤相比,银屑病皮损皮肤中IL-20Rα和IL-20Rβ mRNA水平虽有适度下降,但具有统计学意义。在用卡泊三醇或CsA治疗期间,IL-19和IL-20 mRNA水平随着银屑病的临床改善而下降。在这种短期治疗期间,银屑病皮损皮肤中的IL-19、IL-20以及受体亚基mRNA表达均未达到非皮损皮肤的水平。这些发现与治疗结束时观察到的残留疾病活动情况一致。

结论

银屑病皮损皮肤中IL-19和IL-20 mRNA表达水平升高表明这两种细胞因子在银屑病发病机制中起作用。IL-19和IL-20受体复合物的失衡可能导致它们的致病作用。

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