Groves R W, Mizutani H, Kieffer J D, Kupper T S
Harvard Skin Disease Research Center, Division of Dermatology, Brigham and Women's Hospital, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11874-8. doi: 10.1073/pnas.92.25.11874.
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 evidence 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.
静息状态的表皮角质形成细胞含有大量白细胞介素1（IL-1），但这种细胞因子在皮肤中的功能仍不清楚。为了进一步明确IL-1在皮肤生物学中的作用，我们构建了两系转基因小鼠（TgIL-1.1和TgIL-1.2），它们在基底角质形成细胞中过表达IL-1α。两系小鼠均有高水平的转基因mRNA和蛋白质的组织特异性表达，大量IL-1α从表皮释放进入循环系统。转基因表达水平最高的TgIL-1.1小鼠发生了一种自发性皮肤病，其特征为脱毛、脱屑和局灶性炎症性皮肤病变。组织学上，这些动物的非病变皮肤表现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。炎症病变的特征是混合性细胞浸润、棘层肥厚，在某些情况下还有角化不全。这些发现证实了IL-1作为一种主要细胞因子的概念，其释放能够引发并定位炎症反应。此外，这些小鼠提供了首个确凿证据，即炎症介质可从表皮释放进入体循环，从而以旁分泌或内分泌方式影响多种其他细胞类型。
