Effects of topically applied rapamycin and mycophenolic acid on TNCB-induced atopic dermatitis-like skin lesions in NC/Nga mice
Effects of topically applied rapamycin and mycophenolic acid on TNCB-induced atopic dermatitis-like skin lesions in NC/Nga mice
复制标题
DOI：
10.1016/j.intimp.2015.03.007
复制
发表时间：
2015-06-01
影响因子：
5.6
通讯作者：
Park, Young Min
中科院分区：
文献类型：
--
作者：
Jung, Kyung Eun;Lee, Ye Jin;Park, Young Min
雷帕霉素(RPM)和霉酚酸(MPA)是被批准用于预防移植排斥的免疫抑制剂。这些药物还被用于皮肤科领域，作为糖皮质激素的备用药物，用于治疗自身免疫性和炎症性疾病，如特应性皮炎(AD)。本研究的目的是观察外用RPM和/或MPA对NC/NGA小鼠AD样皮损的治疗作用。以2-氯-1，3，5-三硝基苯(TNCB)诱导的AD样皮肤病变为模型，对NC/NGA小鼠外用RPM(0.04%~4%)、MPA(0.2%~5%)及其不同比例的制剂。通过测量皮肤严重程度评分、耳厚度和皮肤组织学变化(包括肥大细胞计数和血清总IgE水平)，评估局部使用RPM、MPA和混合制剂对经TNCB治疗的NC/NGA小鼠的疗效。局部应用4%RPM和/或1%Mpa可显著改善第29天AD患者的临床症状，如红斑、水肿、脱屑和干燥(P<；0.05)。此外，与赋形剂相比，4%RPM、1%Mpa和混合制剂显著减少了表皮增厚、真皮水肿和细胞渗入真皮。RPM(4%)和/或Mpa(1%)显著降低IL-4和干扰素-γ的mRNA和蛋白表达水平(P<；0.05)。外用4%RPM和/或1%Mpa对血清总IgE水平无明显影响。结果表明，外用4%RPM和/或1%MPA可通过抑制Th2相关细胞因子(IL-4)和Th1相关细胞因子(干扰素-γ)的表达，改善TNCB诱导的NC/NGA小鼠AD样病变。这些发现表明，RPM和/或MPA可能是治疗AD的有前景的局部治疗候选药物。(C)2015爱思唯尔B.V.保留所有权利。
Rapamycin (RPM) and mycophenolic acid (MPA) are immunosuppressive drugs approved for use in preventing transplant rejection. These drugs have also been used in the field of dermatology as glucocorticoid sparing agents for autoimmune and inflammatory disorders such as atopic dermatitis (AD). The aim of this study was to investigate the therapeutic effect of topically applied RPM and/or MPA on AD-like skin lesions in NC/Nga mice. RPM (0.04% - 4%), MPA (0.2% - 5%), and formulations of both agents at various ratios were administrated topically to NC/Nga mice with 2-chloro-1,3,5-trinitrobenzene (TNCB)-induced AD-like skin lesions. The therapeutic effects of topical RPM, MPA, and the mixed formulations in TNCB-treated NC/Nga mice were assessed by measuring skin severity scores, ear thickness, and histological changes in the lesioned skin including mast cell count and total serum IgE levels. Expression of interleukin (IL)-4, and interferon (IFN)-gamma was also assessed.Topical 4% RPM and/or 1% MPA treatment significantly improved clinical signs of AD such as erythema, edema, excoriation, and dryness on day 29 (P < 0.05). In addition, 4% RPM, 1% MPA, and the mixed formulations significantly decreased epidermal thickening, dermal edema, and cellular infiltration into the dermis compared with the vehicle. RPM (4%) and/or MPA (1%) significantly reduced the expression of IL-4 and IFN-gamma mRNA and protein levels compared with the vehicle (P < 0.05). No significant change in the levels of total serum IgE was induced by topical 4% RPM and/or 1% MPA. The present results demonstrated that topical 4% RPM and/or 1% MPA improved TNCB-induced AD-like lesions of NC/Nga mice by suppressing expression of Th2-related cytokines (IL-4) and Th1-related cytokines (IFN-gamma). These findings suggest that RPM and/or MPA may be promising topical therapeutic candidates for the treatment of AD. (C) 2015 Elsevier B.V. All rights reserved.