Local production of prolactin in lesions may play a pathogenic role in psoriatic patients and imiquimod-induced psoriasis-like mouse model
Local production of prolactin in lesions may play a pathogenic role in psoriatic patients and imiquimod-induced psoriasis-like mouse model
复制标题
皮损中催乳素的局部产生可能在银屑病患者和咪喹莫特诱导的银屑病样小鼠模型中发挥致病作用
DOI：
10.1111/exd.13772
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发表时间：
2018
影响因子：
3.6
通讯作者：
Zheng Jie
中科院分区：
文献类型：
--
作者：
Yang Hui;Li Xia;Xue Feng;Xia Qunli;Zhao Xin;Wang Dixin;Chen Lihong;Cao Hua;Xu Han;Shen Xiaoyan;Yuan Weiru;Zhao Xiaoqing;Shi Ruofei;Zheng Jie
人催乳素（PRL）是一种众所周知的泌乳和生殖垂体激素，但它在一些炎症或自身免疫性疾病（包括银屑病）中也具有免疫刺激作用，但尚未得到很好的阐明。本研究旨在通过临床病例对照研究确定PRL与银屑病的关系，并探讨PRL在咪喹莫特（imiquimod，IMQ）诱导的银屑病样小鼠模型发病机制中的作用。收集寻常型银屑病（PsV）患者、红皮病型银屑病患者和健康对照（HC）的血清进行PRL试验。收集皮肤活检组织用于PRL、PRL受体（PRLRs）、细胞因子mRNA水平测定、PRL免疫组织化学和PRL蛋白质印迹。将小鼠分为四组（每组n = 6）：对照组（CON）、IMQ组、抗PRL组和溶剂组。抗PRL组和溶剂组小鼠分别接受PRL拮抗剂（卡麦角林）和溶剂（0.25%甲基纤维素）处理。PsV患者血清PRL水平明显高于HC患者（P< 0.001）。PsV患者皮损组织中PRL和Th 1/Th 17细胞因子的mRNA水平较HCs明显升高（P< 0.05），表皮和真皮组织中PRL蛋白水平也明显升高。在IMQ诱导的银屑病样小鼠模型中，皮损中PRL的mRNA和蛋白水平均显著高于CON组（P< 0.01）。与溶剂组相比，抗PRL组血清PRL水平及皮损组织中PRL、细胞因子mRNA水平均显著降低，皮肤炎症状态也明显减轻。提示局部产生的PRL是皮损中PRL的主要来源，可能在银屑病的皮肤炎症中起重要作用。
Human prolactin (PRL) is a well‐known hormone for pituitary of lactation and reproduction, but it also has immunostimulatory effect in some inflammatory or autoimmune diseases including psoriasis, which has not been well elucidated. This study aimed to determine the relationship between PRL and psoriasis through clinical case‐control studies, and explore the function of PRL in the pathogenesis of imiquimod (IMQ)‐induced psoriasis‐like mouse model. Serum from patients with psoriasis vulgaris (PsV), patients with erythrodermic psoriasis, and healthy controls (HCs) were collected for PRL test. Skin biopsies were collected for PRL, PRL receptors (PRLRs), cytokines mRNA level determination, PRL immunohistochemistry and PRL Western blotting. Mice were divided into four groups (each n = 6): control group (CON), IMQ group, anti‐PRL group and solvent group. Anti‐PRL group and solvent group mice were treated with PRL antagonist (cabergoline) and the solvent (0.25% methylcellulose) separately. The serum PRL level of PsV patients was significantly higher than that of HCs (P< 0.001). Compared with HCs, the mRNA levels of PRL and Th1/Th17 cytokines in skin lesions increased significantly (P< 0.05), and the PRL protein level was also significantly elevated in the epidermis and dermis of PsV patients. In IMQ‐induced psoriasis‐like mouse model, the mRNA and protein levels of PRL in skin lesions were significantly higher than CON group (P< 0.01). Comparing to solvent group, serum PRL level and PRL, cytokines mRNA levels in skin lesions all decreased significantly and the skin inflammatory condition was also alleviated obviously in anti‐PRL group. This study suggests that local production of PRL is the main resource of PRL in skin lesions and may play an important role in skin inflammatory of psoriasis.