Inhibition of keratinocyte apoptosis by IL-15:: A new parameter in the pathogenesis of psoriasis?
Inhibition of keratinocyte apoptosis by IL-15:: A new parameter in the pathogenesis of psoriasis?
复制标题
DOI：
10.4049/jimmunol.165.4.2240
复制
发表时间：
2000-08-15
影响因子：
4.4
通讯作者：
Bulfone-Paus, S
中科院分区：
文献类型：
--
作者：
Rückert, R;Asadullah, K;Bulfone-Paus, S
角质形成细胞（Keratinocytes，KC）是多种细胞因子的重要来源和靶细胞，虽然KC表达IL-15 mRNA，但IL-15对KC的功能影响仍有待进一步研究。研究原代人包皮KC和HaCaT细胞，我们通过半定量RT-PCR和流式细胞术分析显示，在细胞表面都翻译IL-15和IL-15 R mRNA并表达IL-15和IL-15 R α蛋白，这表明人KC可以利用IL-15进行阿曲他克林信号传导。虽然IL-15对KC增殖和IL-6或IL-8分泌没有显著影响，但IL-15在体外抑制抗Fas和甲基纤维素诱导的KC凋亡。这与公认的IL-15的有效抗凋亡作用一致。IL-2的受体与IL-15 R共享两个组分，但不能抑制KC凋亡。与IL-15在维持慢性免疫反应中的作用一起，这引起了这样的问题：IL-15引起的KC凋亡的减少是否可能参与银屑病的发病机制，银屑病是一种慢性过度增殖性炎症性皮肤病，其特征在于表皮中KC凋亡异常低。值得注意的是，与非皮损性银屑病皮肤和健康志愿者的皮肤相比，皮损性银屑病表皮在表皮中显示出高IL-15蛋白表达，并增强了IL-15的结合活性。因此，拮抗IL-15对KC凋亡的抑制作用值得探索作为银屑病管理的新的治疗策略。
Keratinocytes (KC) are important source of and targets for several cytokines, Although KC express IL-15 mRNA, the functional effects of IL-15 on these epithelial cells remain to be dissected. Investigating primary human foreskin KC and HaCaT cells, we show here by semiquantitative RT-PCR and flow cytometric analysis that both translate IL-15 and IL-15R mRNA and express IL-15 and IL-15R alpha protein on the cell surface, suggesting that human KC can employ IL-15 for juxtacrine signaling. While IL-15 exerted no significant effect on KC proliferation and IL-6 or IL-8 secretion, IL-15 inhibited both anti-Fas and methylcellulose-induced KC apoptosis in vitro. This is in line with the recognized potent anti-apoptotic effects of IL-15. IL-2, whose receptor shares two components with the IL-15R, failed to inhibit KC apoptosis. Together with the role of IL-15 in sustaining chronic immune reactions, this invited the question of whether a reduction of KC apoptosis by IL-15 may be involved in the pathogenesis of psoriasis, a chronic hyperproliferative inflammatory skin disease characterized by abnormally low KC apoptosis in the epidermis. Remarkably, compared with nonlesional psoriatic skin and skin of healthy volunteers, lesional psoriatic epidermis showed high IL-15 protein expression in the epidermis and enhanced binding activity for IL-15. Therefore, antagonizing the inhibitory effects of IL-15 on KC apoptosis deserves exploration as a novel therapeutic strategy in psoriasis management.