Abstract:
Interleukin (IL)-22 is a pro-inflammatory cytokine driving the progression of the psoriatic lesion with other cytokines, as Tumor Necrosis Factor (TNF)-alpha and IL-17. Our study was aimed at evaluating the early effect of IL-22 alone or in combination with TNF-alpha and IL-17 by immunofluorescence on i) keratinocyte (KC) proliferation, ii) terminal differentiation biomarkers as keratin (K) 10 and 17 expression, iii) intercellular junctions. Transmission electron microscopy (TEM) analysis was performed. A model of human skin culture reproducing a psoriatic microenvironment was used. Plastic surgery explants were obtained from healthy young women (n=7) after informed consent. Fragments were divided before adding IL-22 or a combination of the three cytokines, and harvested 24 (T24), 48 (T48), and 72 (T72)h later. From T24, in IL-22 samples we detected a progressive decrease in K10 immunostaining in the spinous layer paralleled by K17 induction. By TEM, after IL-22 incubation, keratin aggregates were evident in the perinuclear area. Occludin immunostaining was not homogeneously distributed. Conversely, KC proliferation was not inhibited by IL-22 alone, but only by the combination of cytokines. Our results suggest that IL-22 affects keratinocyte terminal differentiation, whereas, in order to induce a proliferation impairment, a more complex psoriatic-like microenvironment is needed.
摘要:
白细胞介素(IL)-22是一种促炎细胞因子,与其他细胞因子一起驱动银屑病病变的进展,肿瘤坏死因子(TNF)-α和IL-17。我们的研究旨在通过免疫荧光评估IL-22单独或与TNF-α和IL-17联合对i)角质形成细胞(KC)增殖的早期作用,ii)终末分化生物标志物如角蛋白(K)10和17表达,iii)细胞间连接。进行透射电子显微镜(TEM)分析。使用了复制牛皮癣微环境的人类皮肤培养模型。在知情同意后,从健康的年轻女性(n=7)获得整形手术外植体。在添加IL-22或三种细胞因子的组合之前,将片段分开,收获24(T24),48(T48),和72(T72)h后。从T24开始,在IL-22样品中,我们检测到棘层中K10免疫染色的逐渐降低与K17诱导平行。通过TEM,IL-22孵育后,角蛋白聚集体在核周区域很明显。Occludin免疫染色不均匀分布。相反,KC增殖不被单独的IL-22抑制,但只能通过细胞因子的组合。我们的结果表明,IL-22影响角质形成细胞的终末分化,然而,为了诱导增殖受损,需要一个更复杂的牛皮癣样的微环境。