Efficacy of combined peroxisome proliferator-activated receptor-α ligand and glucocorticoid therapy in a murine model of atopic dermatitis.
Efficacy of combined peroxisome proliferator-activated receptor-α ligand and glucocorticoid therapy in a murine model of atopic dermatitis.
复制标题
DOI：
10.1038/jid.2011.144
复制
发表时间：
2011-09
影响因子：
6.5
通讯作者：
Fujiwara, Sakuhei
中科院分区：
文献类型：
--
作者：
Hatano, Yutaka;Elias, Peter M.;Crumrine, Debra;Feingold, Kenneth R.;Katagiri, Kazumoto;Fujiwara, Sakuhei
虽然局部糖皮质激素（GC）在发炎的皮肤中显示出有效的抗炎活性，但它们也会对表皮结构和功能产生许多有害影响。相比之下，局部应用过氧化物酶体增殖物激活受体-α（PPARα）配体不仅可以减轻炎症，还可以改善皮肤屏障的稳态。因此，我们在具有多种AD特征的半抗原（恶唑酮）诱导的小鼠模型（Ox-AD）中检查了序贯局部GC后局部Wy 14643（PPARα的配体）是否比单独使用更有效。尽管有预期的抗炎益处，但局部GC单独诱导：i）表皮变薄; ii）外皮蛋白、兜甲蛋白和聚丝蛋白的表达减少;和iii）允许表皮示踪剂由外向内渗透。虽然Wy 14643单独在患有轻度或中度Ox-AD的小鼠中产生显著的治疗益处，但在重度Ox-AD中效果较差。然而，GC后局部应用Wy 14643不仅与单独GC相比具有显著的有效性，而且还防止了GC诱导的渗透性屏障稳态的结构和功能异常。此外，GC和Wy 14643序贯治疗后，反弹耀斑基本消失。总之，这些结果表明GC和PPARα配体联合治疗不仅有效，而且可预防小鼠AD中GC诱导的副作用（包括反弹发作）的发生。
Although topical glucocorticoids (GCs) display potent anti-inflammatory activity in inflamed skin, they also can exert numerous harmful effects on epidermal structure and function. In contrast, topical applications of ligands of peroxisome proliferator-activated receptor-α (PPARα) not only reduce inflammation, and also improve cutaneous barrier homeostasis. Therefore, we examined whether sequential topical GCs followed by topical Wy14643 (a ligand of PPARα) might be more effective than either alone for atopic dermatitis (AD) in a hapten (oxazolone)-induced, murine model with multiple features of AD (Ox-AD). Despite expected anti-inflammatory benefits, topical GC alone induced: i) epidermal thinning; ii) reduced expression of involucrin, loricrin and filaggrin; and iii) allowed outside-to-inside penetration of an epicutaneous tracer. While Wy14643 alone yielded significant therapeutic benefits in mice with mild or moderate Ox-AD, it was less effective in severe Ox-AD. Yet, topical applications of Wy14643 after GC was not only significantly effective comparable to GC alone, but it also prevented GC-induced structural and functional abnormalities in permeability barrier homeostasis. Moreover, rebound flares were largely absent after sequential treatment with GC and Wy14643. Together, these results show that GC and PPARα ligand therapy together is not only effective but also prevents development of GC-induced side effects, including rebound flares, in murine AD.
登录
查看更多内容
影响因子：
14.2
作者：
Scharschmidt, Tiffany C.;Man, Mao-Qiang;Hatano, Yutaka;Crumrine, Debra;Gunathilake, Roshan;Sundberg, John P.;Silva, Kathleen A.;Mauro, Theodora M.;Hupe, Melanie;Cho, Soyun;Wu, Yan;Celli, Anna;Schmuth, Matthias;Feingold, Kenneth R.;Elias, Peter M.
通讯作者：
Elias, Peter M.
影响因子：
6.5
作者：
Man, Mao-Qiang;Hatano, Yutaka;Elias, Peter M.
通讯作者：
Elias, Peter M.
影响因子：
6.5
作者：
Kömüves, LG;Hanley, K;Feingold, KR
通讯作者：
Feingold, KR
影响因子：
10.3
作者：
Angelova-Fischer, I;Bauer, A;Fluhr, JW
通讯作者：
Fluhr, JW
影响因子：
6.5
作者：
Ashida, Y;Denda, M;Hirao, T
通讯作者：
Hirao, T