Seo Hee-Seok, Seong Ki Hyun, Kim Chang-Deok, Seo Seong Jun, Park Byung Cheol, Kim Myung Hwa, Hong Seung-Phil
Department of Dermatology, Dankook University College of Medicine, Cheonan, Korea.
Department of Dermatology, Chungnam National University College of Medicine, Daejeon, Korea.
Ann Dermatol. 2019 Apr;31(2):186-195. doi: 10.5021/ad.2019.31.2.186. Epub 2019 Feb 28.
Atopic dermatitis (AD) is a chronic disorder, with a vicious cycle of repetitive inflammation and deterioration of the epidermal barrier function. Adiponectin, an adipokine, has anti-inflammatory effects on various metabolic and inflammatory disorders. Recently, its level was found to be reduced in serum and tissue samples from AD patients.
We aimed to investigate the effects of adiponectin on epidermal inflammation and barrier structures in AD skin.
A three-dimensional epidermal equivalent model mimicking AD was obtained by adding an inflammatory substance cocktail to normal human epidermal equivalents (HEEs). The expression of epidermal differentiation markers, primary inflammatory mediators, and lipid biosynthetic enzymes was compared between adiponectintreated AD-HEEs, untreated control AD-HEEs, and normal HEEs.
Adiponectin co-treatment 1) inhibited the increase in mRNA expression of major inflammatory mediators (carbonic anhydrase II, neuron-specific NEL-like protein 2, thymic stromal lymphopoietin, interleukin-8, tumor necrosis factor-alpha, and human beta-defensin-2) from keratinocytes in AD-inflammatory HEEs, 2) enhanced the expression of lipid biosynthetic enzymes (fatty acid synthase, HMG CoA reductase, and serine-palmitoyl transferase), and 3) promoted the expression of differentiation factors, especially filaggrin. We also found that the expression of adiponectin receptor-1 and -2 decreased in the epidermis of chronic AD lesion.
Activation of the adiponectin pathway is expected to enhance epidermal differentiation and barrier function as well as attenuate inflammatory response to AD as a therapeutic approach.
特应性皮炎（AD）是一种慢性疾病，存在反复炎症和表皮屏障功能恶化的恶性循环。脂联素作为一种脂肪因子，对各种代谢和炎症性疾病具有抗炎作用。最近发现，AD患者血清和组织样本中脂联素水平降低。
我们旨在研究脂联素对AD皮肤表皮炎症和屏障结构的影响。
通过向正常人表皮等效物（HEEs）中添加炎症物质混合物获得模拟AD的三维表皮等效模型。比较脂联素处理的AD-HEEs、未处理的对照AD-HEEs和正常HEEs之间表皮分化标志物、主要炎症介质和脂质生物合成酶的表达。
脂联素联合处理1）抑制了AD炎症性HEEs中角质形成细胞主要炎症介质（碳酸酐酶II、神经元特异性NEL样蛋白2、胸腺基质淋巴细胞生成素、白细胞介素-8、肿瘤坏死因子-α和人β-防御素-2）mRNA表达的增加，2）增强了脂质生物合成酶（脂肪酸合酶、HMG CoA还原酶和丝氨酸-棕榈酰转移酶）的表达，3）促进了分化因子的表达，尤其是丝聚合蛋白。我们还发现，慢性AD病变表皮中脂联素受体-1和-2的表达降低。
激活脂联素途径有望增强表皮分化和屏障功能，并减轻对AD的炎症反应，作为一种治疗方法。
