Psoriasis genomics: analysis of proinflammatory (type 1) gene expression in large plaque (Western) and small plaque (Asian) psoriasis vulgaris
Psoriasis genomics: analysis of proinflammatory (type 1) gene expression in large plaque (Western) and small plaque (Asian) psoriasis vulgaris
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DOI：
10.1111/j.0007-0963.2004.05891.x
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发表时间：
2004-04-01
影响因子：
10.3
通讯作者：
Krueger, JG
中科院分区：
文献类型：
--
作者：
Lew, W;Lee, E;Krueger, JG
背景1型T细胞被认为在银屑病的免疫发病机制中起中心作用。通过干扰素-γ的表达，1型T细胞调节许多“下游”炎症基因的表达，包括一系列调节皮肤病变中白细胞运输和激活的趋化因子。因此，疾病的进展和/或严重程度可能由不同的细胞因子和趋化因子在局部皮肤区域过度表达的程度控制。为了检验这种可能性，我们研究了两种在总体严重程度和进展方面有显著差异的慢性寻常型银屑病：发生在韩国患者的小斑块(SP)银屑病，以及发生在北美患者的大斑块(LP)银屑病。目的研究寻常型银屑病和大斑块(LP)银屑病皮损中定义I型T细胞轴的促炎基因[编码白介素12(IL)-12、干扰素-γ(IFN-γ)、方法采用定量逆转录-聚合酶链式反应(TaqMan分析)技术，对寻常型银屑病和寻常型银屑病患者皮肤组织中角蛋白16、CD25、干扰素-γ、IL-12p40、信号转导和转录激活子-1、诱导型一氧化氮合酶、IL-8、巨噬细胞炎性蛋白-3α、单核细胞趋化蛋白-1、S100A12、10 kDa干扰素-γ诱导蛋白的mRNA表达进行分析。在寻常型银屑病和寻常型银屑病皮损中，干扰素诱导的T细胞α趋化因子和单核细胞因子均升高。结论IL-18基因在寻常型银屑病和寻常型银屑病皮损中的表达差异有统计学意义。结论IL-18在寻常型银屑病和寻常型银屑病皮损中的表达差异显著。这组基因的持续激活证明了干扰素-γ作为这些不同亚型寻常型牛皮癣炎症的分子调节因子的核心作用。相比之下，疾病的程度/严重程度必须由其他因素控制。
Background Type 1 T cells are hypothesized to be central in the immunopathogenesis of psoriasis. Through elaboration of interferon (IFN)-gamma, type 1 T cells regulate the expression of many 'downstream' inflammatory genes, including an array of chemokines that regulate leucocyte trafficking and activation in skin lesions. Accordingly, disease progression and/or severity might be controlled by the degree to which differing cytokines and chemokines are overexpressed in focal skin regions. To examine this possibility, we studied two forms of chronic psoriasis vulgaris that differ significantly in overall severity and progression: small plaque (SP) psoriasis occurring in Korean patients, and large plaque (LP) psoriasis occurring in North American patients.Objectives To characterize LP and SP psoriasis vulgaris with respect to expression of proinflammatory genes that define the type I T-cell axis in skin lesions [genes encoding interleukin (IL)-12, IFN-gamma, and IFN-gamma-regulated chemokines or inflammatory mediators].Methods Total cellular RNA of skin samples from groups of patients with LP or SP psoriasis was analysed by quantitative reverse transcription-polymerase chain reaction (TaqMan analysis) to compare the differences in mRNA expression of genes related to the IFN-gamma pathway.Results The mRNA expression of keratin 16, CD25, IFN-gamma, IL-12 p40, signal transducer and activator of transcription-1, inducible nitric oxide synthase, IL-8, macrophage inflammatory protein-3alpha, monocyte chemoattractant protein-1, S100A12, IFN-gamma-inducible protein of 10 kDa, IFN-inducible T-cell alpha-chemoattractant and monokine induced by IFN-gamma was increased in the lesions of both LP psoriasis and SP psoriasis. However, IL-18 mRNA expression was significantly different in the lesions of LP psoriasis in comparison with those of SP psoriasis.Conclusions The results indicate that proinflammatory type I genes regulated by IFN-gamma are similarly increased in both SP and LP psoriasis, but a potential difference in IL-18 exists between these disease forms. The consistent activation of this set of genes argues for a central role of IFN-gamma as a molecular regulator of inflammation in these distinct subtypes of psoriasis vulgaris. In contrast, disease extent/severity must be controlled by yet other factors.