Nomura Ichiro, Gao Bifeng, Boguniewicz Mark, Darst Marc A, Travers Jeffrey B, Leung Donald Y m
Department Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.
J Allergy Clin Immunol. 2003 Dec;112(6):1195-202. doi: 10.1016/j.jaci.2003.08.049.
Atopic dermatitis (AD) and psoriasis are the two most common chronic inflammatory skin diseases. Both of these diseases have distinct clinical findings and specific inflammatory cell infiltrates. Previous reports have focused individually on one or two genes or gene products in the lesions of both skin diseases. However, they have not captured the complex gene expression that must occur to induce specific cellular infiltrates in the skin lesions of these two diseases. DNA microarray studies allow the simultaneous comparison of thousands of messenger RNAs that may identify the disease-specific pattern of tissue inflammatory responses.
To compare the complex gene expression pattern of AD versus psoriasis skin lesions.
RNA was extracted from skin biopsy specimens of 6 patients with AD and 7 patients with psoriasis and analyzed with the use of Hu-U95Av.GeneChip microarrays. To confirm GeneChip results, real-time PCR of selected genes were performed.
In AD skin, a total of 18 genes including the CC chemokines, CCL-13/MCP-4, CCL-18/PARC, and CCL-27/CTACK showed a statistically significant, >2-fold increase of gene expression compared with psoriasis. In psoriasis skin, a total of 62 genes including CCL-4/MIP-1beta, CCL-20/MIP-3alpha, CXCL-2/GRO-beta CXCL-8/IL-8, and CXCR2/IL-8R showed a >2-fold increase of gene expression compared with AD skin. Real-time PCR confirmed several of these GeneChip results.
These results show a very distinctive gene expression pattern in AD as compared with psoriasis that may explain several features of AD and psoriasis including the specific inflammatory cell infiltrates observed in these disorders, that is, T(H)2 cells, eosinophils, and mast cells in AD and T(H)1 cells and neutrophils in psoriasis. Such observations may contribute to a characteristic "signature" for these two skin diseases.
特应性皮炎(AD)和银屑病是两种最常见的慢性炎症性皮肤病。这两种疾病都有独特的临床表现和特定的炎症细胞浸润。既往报道分别聚焦于这两种皮肤病皮损中的一两个基因或基因产物。然而,它们并未捕捉到诱导这两种疾病皮损中特定细胞浸润所必需的复杂基因表达。DNA微阵列研究允许同时比较数千种信使RNA,这可能识别出疾病特异性的组织炎症反应模式。
比较AD与银屑病皮损的复杂基因表达模式。
从6例AD患者和7例银屑病患者的皮肤活检标本中提取RNA,并使用Hu-U95Av.GeneChip微阵列进行分析。为了证实基因芯片结果,对选定基因进行了实时PCR。
在AD皮肤中,包括CC趋化因子CCL-13/MCP-4、CCL-18/PARC和CCL-27/CTACK在内的总共18个基因,与银屑病相比,基因表达有统计学意义的>2倍增加。在银屑病皮肤中,包括CCL-4/MIP-1β、CCL-20/MIP-3α、CXCL-2/GRO-β、CXCL-8/IL-8和CXCR2/IL-8R在内的总共62个基因,与AD皮肤相比,基因表达有>2倍增加。实时PCR证实了这些基因芯片结果中的几个。
这些结果显示,与银屑病相比,AD有非常独特的基因表达模式,这可能解释了AD和银屑病的几个特征,包括在这些疾病中观察到的特定炎症细胞浸润,即AD中的Th2细胞、嗜酸性粒细胞和肥大细胞,以及银屑病中的Th1细胞和中性粒细胞。这些观察结果可能有助于为这两种皮肤病确定特征性的“特征”。