Stjernholm Theresa, Ommen Pernille, Langkilde Ane, Johansen Claus, Iversen Lars, Rosada Cecilia, Stenderup Karin
Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.
Exp Dermatol. 2017 Apr;26(4):338-345. doi: 10.1111/exd.13149. Epub 2016 Dec 2.
Leptin is an adipocyte-derived cytokine secreted mostly by adipose tissue. Serum leptin levels are elevated in obese individuals and correlate positively with body mass index (BMI). Interestingly, serum leptin levels are also elevated in patients with psoriasis and correlate positively with disease severity. Psoriasis is associated with obesity; patients with psoriasis have a higher incidence of obesity, and obese individuals have a higher risk of developing psoriasis. Additionally, obese patients with psoriasis experience a more severe degree of psoriasis. In this study, we hypothesised that leptin may link psoriasis and obesity and plays an aggravating role in psoriasis. To investigate leptin's role in psoriasis, we applied the widely accepted imiquimod (IMQ)-induced psoriasis-like skin inflammation mouse model on leptin-deficient (ob/ob) mice and evaluated psoriasis severity. Moreover, we stimulated human keratinocytes with leptin and investigated the effect on proliferation and expression of pro-inflammatory proteins. In ob/ob mice, clinical signs of erythema, infiltration and scales in dorsal skin and inflammation in ear skin, as measured by ear thickness, were attenuated and compared with wt mice. Moreover, IL-17A and IL-22 mRNA expression levels, as well as increased epidermal thickness, were significantly less induced. In vitro, the effect of leptin stimulation on human keratinocytes demonstrated increased proliferation and induced secretion of several pro-inflammatory proteins; two hallmarks of psoriasis. In conclusion, leptin deficiency attenuated IMQ-induced psoriasis-like skin inflammation in a mouse model, and leptin stimulation induced a pro-inflammatory phenotype in human keratinocytes, thus, supporting an aggravating role of leptin in psoriasis.
瘦素是一种主要由脂肪组织分泌的脂肪细胞衍生细胞因子。肥胖个体的血清瘦素水平升高，且与体重指数（BMI）呈正相关。有趣的是，银屑病患者的血清瘦素水平也升高，且与疾病严重程度呈正相关。银屑病与肥胖相关；银屑病患者肥胖发生率更高，而肥胖个体患银屑病的风险更高。此外，肥胖的银屑病患者银屑病程度更严重。在本研究中，我们假设瘦素可能将银屑病和肥胖联系起来，并在银屑病中起加重作用。为了研究瘦素在银屑病中的作用，我们在瘦素缺乏（ob/ob）小鼠上应用了广泛接受的咪喹莫特（IMQ）诱导的银屑病样皮肤炎症小鼠模型，并评估银屑病严重程度。此外，我们用瘦素刺激人角质形成细胞，并研究其对增殖和促炎蛋白表达的影响。在ob/ob小鼠中，背部皮肤的红斑、浸润和鳞屑的临床体征以及耳部皮肤炎症（通过耳厚度测量）与野生型小鼠相比有所减轻。此外，IL-17A和IL-22 mRNA表达水平以及表皮厚度增加均明显减少。在体外，瘦素刺激对人角质形成细胞的影响表现为增殖增加和几种促炎蛋白的分泌诱导增加；这是银屑病的两个标志。总之，瘦素缺乏减轻了小鼠模型中IMQ诱导的银屑病样皮肤炎症，而瘦素刺激在人角质形成细胞中诱导了促炎表型，因此，支持瘦素在银屑病中起加重作用。
