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局部产生的催乳素在皮损中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。

Local production of prolactin in lesions may play a pathogenic role in psoriatic patients and imiquimod-induced psoriasis-like mouse model.

机构信息

Department of Dermatology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Laboratory of Dermatoimmunology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Exp Dermatol. 2018 Nov;27(11):1245-1253. doi: 10.1111/exd.13772. Epub 2018 Sep 19.

DOI:10.1111/exd.13772
PMID:30120801
Abstract

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.

摘要

人催乳素(PRL)是一种众所周知的催乳素和生殖腺垂体激素,但它在一些炎症或自身免疫性疾病中也具有免疫刺激作用,包括银屑病,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来确定 PRL 与银屑病之间的关系,并探索 PRL 在咪喹莫特(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 检测。采集皮肤活检标本,用于 PRL、PRL 受体(PRLRs)、细胞因子 mRNA 水平测定、PRL 免疫组化和 PRL Western blot。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用 PRL 拮抗剂(卡麦角林)和溶剂(0.25%甲基纤维素)处理。PsV 患者的血清 PRL 水平明显高于 HCs(P<0.001)。与 HCs 相比,皮肤病变中 PRL 和 Th1/Th17 细胞因子的 mRNA 水平显著升高(P<0.05),PRL 蛋白水平在 PsV 患者的表皮和真皮中也显著升高。在 IMQ 诱导的银屑病样小鼠模型中,皮肤病变中的 PRL mRNA 和蛋白水平明显高于 CON 组(P<0.01)。与溶剂组相比,抗 PRL 组血清 PRL 水平和皮肤病变中 PRL、细胞因子 mRNA 水平均显著降低,皮肤炎症状况也明显缓解。本研究表明,皮肤病变中 PRL 的局部产生是皮肤病变中 PRL 的主要来源,可能在银屑病的皮肤炎症中发挥重要作用。

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