Psoriasis Research and Treatment Centre, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany; Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany; Berlin-Brandenburg Centre for Regenerative Therapies, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
Department of Dermatology, University of Luebeck, Ratzeburger Allee 160, 23538 Luebeck, Germany.
J Dermatol Sci. 2018 Apr;90(1):68-74. doi: 10.1016/j.jdermsci.2017.12.018. Epub 2018 Jan 11.
Palmoplantar pustular psoriasis (PPP) is a recalcitrant chronic skin disease affecting the palms and soles.
To identify and characterize pathogenetic players in PPP.
Clinical and anamnestic data as well as skin and blood samples of 60 PPP patients were collected. Healthy participants served as controls. Analysis of patient samples and cultured primary skin cells was performed by ELISA, qRT-PCR, and immunohistochemistry.
Upon screening of blood mediators in PPP patients, lipocalin 2 (LCN2) emerged as being significantly upregulated compared to healthy participants. LCN2 blood levels were independent of age, sex, or concomitant psoriasis vulgaris. Keratinocytes in PPP skin lesions were important LCN2 producers. In vitro, LCN2 production of these cells was upregulated by IL-1β and further enhanced by IL-17 and TNF-α, while IL-22 had no effect. Accordingly, a positive relationship between blood IL-1β and LCN2 levels was evident in PPP. LCN2 blood levels also showed a positive correlation with PPP pustule score, Dermatology Quality of Life Index and blood levels of the pro-atherogenic molecule resistin.
In PPP, increased blood levels of LCN2 indicate an important activity of IL-1β in the epidermis, may contribute to skin neutrophil infiltration, and may point to an increased pro- atherosclerosis risk.
掌跖脓疱病（PPP）是一种影响手掌和脚底的难治性慢性皮肤病。
确定和描述 PPP 的发病机制。
收集了 60 名 PPP 患者的临床和病史数据以及皮肤和血液样本。健康参与者作为对照。通过 ELISA、qRT-PCR 和免疫组织化学分析患者样本和培养的原代皮肤细胞。
在 PPP 患者的血液介质筛选中，发现载脂蛋白 2（LCN2）明显上调，与健康参与者相比。LCN2 血液水平与年龄、性别或并发寻常型银屑病无关。PPP 皮肤病变中的角质形成细胞是重要的 LCN2 产生细胞。在体外，这些细胞的 LCN2 产生被 IL-1β 上调，并进一步被 IL-17 和 TNF-α增强，而 IL-22 没有影响。因此，PPP 中明显存在血液 IL-1β 和 LCN2 水平之间的正相关关系。LCN2 血液水平也与 PPP 脓疱评分、皮肤病生活质量指数和促动脉粥样硬化分子抵抗素的血液水平呈正相关。
在 PPP 中，LCN2 血液水平升高表明表皮中 IL-1β 的重要活性，可能有助于皮肤中性粒细胞浸润，并可能表明动脉粥样硬化风险增加。
