Lew W, Lee E, Krueger J G
Department of Dermatology, Yonsei University College of Medicine, Yongdong Severance Hospital, 146-92 Dogok-Dong, Kangnam-Ku, Seoul, Korea.
Br J Dermatol. 2004 Apr;150(4):668-76. doi: 10.1111/j.0007-0963.2004.05891.x.
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.
To characterize LP and SP psoriasis vulgaris with respect to expression of proinflammatory genes that define the type 1 T-cell axis in skin lesions [genes encoding interleukin (IL)-12, IFN-gamma, and IFN-gamma-regulated chemokines or inflammatory mediators].
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.
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.
The results indicate that proinflammatory type 1 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.
1型T细胞被认为在银屑病的免疫发病机制中起核心作用。通过分泌γ干扰素（IFN-γ），1型T细胞调节许多“下游”炎症基因的表达，包括一系列调节白细胞在皮肤病变部位迁移和激活的趋化因子。因此，疾病的进展和/或严重程度可能受不同细胞因子和趋化因子在局部皮肤区域过度表达程度的控制。为检验这种可能性，我们研究了两种慢性寻常型银屑病，它们在总体严重程度和进展方面有显著差异：韩国患者中的小斑块（SP）型银屑病和北美患者中的大斑块（LP）型银屑病。
通过检测皮肤病变中定义1型T细胞轴的促炎基因（编码白细胞介素（IL）-12、IFN-γ以及IFN-γ调节的趋化因子或炎症介质的基因）的表达，对LP和SP寻常型银屑病进行特征描述。
采用定量逆转录聚合酶链反应（TaqMan分析）对LP或SP银屑病患者组皮肤样本的总细胞RNA进行分析，以比较与IFN-γ途径相关基因的mRNA表达差异。
LP银屑病和SP银屑病皮损中角蛋白16、CD25、IFN-γ、IL-12 p40、信号转导子和转录激活子-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的IFN-γ诱导蛋白、IFN诱导的T细胞α趋化因子以及IFN-γ诱导的单核因子的mRNA表达均增加。然而，与SP银屑病皮损相比，LP银屑病皮损中IL-18 mRNA表达有显著差异。
结果表明，在SP和LP银屑病中，受IFN-γ调节的促炎1型基因同样上调，但这两种疾病形式在IL-18方面存在潜在差异。这一组基因的持续激活表明IFN-γ作为这些不同寻常型银屑病亚型炎症分子调节因子的核心作用。相比之下，疾病范围/严重程度必定受其他因素控制。
