INFLAMMATORY SKIN-DISEASE IN TRANSGENIC MICE THAT EXPRESS HIGH-LEVELS OF INTERLEUKIN-1-ALPHA IN BASAL EPIDERMIS
INFLAMMATORY SKIN-DISEASE IN TRANSGENIC MICE THAT EXPRESS HIGH-LEVELS OF INTERLEUKIN-1-ALPHA IN BASAL EPIDERMIS
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DOI：
10.1073/pnas.92.25.11874
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发表时间：
1995-12-05
影响因子：
11.1
通讯作者：
KUPPER, TS
中科院分区：
文献类型：
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作者：
GROVES, RW;MIZUTANI, H;KUPPER, TS
静止的表皮角质形成细胞含有大量的白细胞介素1（IL-1），但这种细胞因子在皮肤中的功能仍不清楚。为了进一步确定IL-1在皮肤生物学中的作用，我们已经产生了两种在基底角质形成细胞中过表达IL-1 α的转基因小鼠品系（TgIL-1.1和TgIL-1.2）。在两个品系中，转基因mRNA和蛋白质都有高水平的组织特异性表达，并且大量的IL-1 α从表皮释放到循环中。具有最高水平的转基因表达的TgIL-1.1小鼠发生了自发性皮肤病，其特征在于脱发、鳞屑和局灶性炎性皮肤病变。在组织学上，这些动物的非病变皮肤的特征为角化过度和巨噬细胞/单核细胞谱系的真皮单核细胞浸润，炎性病变以混合细胞浸润、棘皮症和角化不全为标志。这些发现证实了IL-1作为主要细胞因子的概念，IL-1的释放能够启动和定位炎症反应。此外，这些小鼠提供了第一个明确的证据，即炎症介质可以从表皮释放进入体循环，从而以旁分泌或内分泌方式影响各种其他细胞类型。
Resting epidermal keratinocytes contain large amounts of interleukin 1 (IL-1), but the function of this cytokine in the skin remains unclear. To further define the role of IL-1 in cutaneous biology, we have generated two lines of transgenic mice (TgIL-1.1 and TgIL-1.2) which overexpress IL-1 alpha in basal keratinocytes. There was high-level tissue-specific expression of transgene mRNA and protein and large quantities of IL-1 alpha were liberated into the circulation from epidermis in both lines. TgIL-1.1 mice, which had the highest level of transgene expression, developed a spontaneous skin disease characterized by hair loss, scaling, and focal inflammatory skin lesions. Histologically, nonlesional skin of these animals was characterized by hyperkeratosis and a dermal mononuclear cell infiltrate of macrophage/monocyte lineage, inflammatory lesions were marked by a mixed cellular infiltrate, acanthosis, and, in some cases, parakeratosis. These findings confirm the concept of IL-1 as a primary cytokine, release of which is able to initiate and localize an inflammatory reaction. Furthermore, these mice provide the first definitive ev,idence that inflammatory mediators can be released from the epidermis to enter the systemic circulation and thereby influence, in a paracrine or endocrine fashion, a wide variety of other cell types.