Sur Bongjun, Lee Bombi, Yoon Ye Seul, Lim Pooreum, Hong Riwon, Yeom Mijung, Lee Hyang Sook, Park Hijoon, Shim Insop, Lee Hyejung, Jang Young Pyo, Hahm Dae-Hyun
Acupuncture and Meridian Science Research Center, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea.
Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, Seoul 02447, Korea.
Int J Mol Sci. 2017 Jan 18;18(1):190. doi: 10.3390/ijms18010190.
Atopic dermatitis (AD) and stress create a vicious cycle: stress exacerbates atopic symptoms, and atopic disease elicits stress and anxiety. Targeting multiple pathways including stress and allergic inflammation is, therefore, important for treating AD. In this study, we investigated the remedial value of Willd. (PTW) for treating immobilization (IMO) stress-exacerbated atopy-like skin dermatitis and its underlying mechanism. Trimellitic anhydride (TMA) was applied to dorsal skin for sensitization and subsequently both ears for eliciting T-cell-dependent contact hypersensitivity in mice, which underwent 2 h-IMO stress and PTW administration for the latter 6 and 9 days in the ear exposure period of TMA, respectively. To elicit in vitro degranulation of human mast cell line-1 (HMC-1), 10 µM substance P (SP) and 200 nM corticotrophin-releasing factor (CRF) were sequentially added with 48 h-interval. PTW extract (500 µg/mL) was added 30 min before CRF treatment. IMO stress exacerbated TMA-induced scratching behavior by 252%, and increased their blood corticosterone levels by two-fold. Treatment with 250 mg/kg PTW significantly restored IMO stress-exacerbated scratching behavior and other indicators such as skin inflammation and water content, lymph node weights, and serum histamine and immunoglobulin E (lgE) levels. Furthermore, it also reversed TMA-stimulated expression of tumor necrosis factor (TNF)-α and interleukin (IL)-4 mRNAs in ear tissues. PTW significantly inhibited SP/CRF-stimulated degranulation of HMC-1 cells, subsequent tryptase secretion, and protein kinase A (PKA) activity. PTW also selectively inhibited p38 mitogen-activated protein kinase (MAPK) phosphorylation in SP/CRF-treated HMC-1 cells. PTW significantly inhibited HMC-1 cell degranulation and alleviated IMO stress-exacerbated atopic dermatitis symptoms by modulating the PKA/p38 MAPK signaling pathway.
特应性皮炎（AD）与压力形成恶性循环：压力会加剧特应性症状，而特应性疾病会引发压力和焦虑。因此，针对包括压力和过敏性炎症在内的多种途径对于治疗AD至关重要。在本研究中，我们调查了威尔德（PTW）对治疗固定（IMO）应激加剧的类特应性皮肤皮炎的补救价值及其潜在机制。将偏苯三酸酐（TMA）应用于背部皮肤进行致敏，随后应用于双耳以引发小鼠T细胞依赖性接触性超敏反应，在TMA耳部暴露期的后6天和9天，分别对小鼠进行2小时的IMO应激和PTW给药。为了引发人肥大细胞系-1（HMC-1）的体外脱颗粒，以48小时间隔依次添加10μM P物质（SP）和200 nM促肾上腺皮质激素释放因子（CRF）。在CRF处理前30分钟加入PTW提取物（500μg/mL）。IMO应激使TMA诱导的抓挠行为加剧了252%，并使其血液皮质酮水平增加了两倍。用250mg/kg PTW治疗可显著恢复IMO应激加剧的抓挠行为以及其他指标，如皮肤炎症和含水量、淋巴结重量以及血清组胺和免疫球蛋白E（IgE）水平。此外，它还逆转了TMA刺激的耳部组织中肿瘤坏死因子（TNF）-α和白细胞介素（IL）-4 mRNA的表达。PTW显著抑制SP/CRF刺激的HMC-1细胞脱颗粒、随后的类胰蛋白酶分泌和蛋白激酶A（PKA）活性。PTW还选择性抑制SP/CRF处理的HMC-1细胞中p38丝裂原活化蛋白激酶（MAPK）的磷酸化。PTW通过调节PKA/p38 MAPK信号通路显著抑制HMC-1细胞脱颗粒并减轻IMO应激加剧的特应性皮炎症状。
