Activators of PPARs and LXR decrease the adverse effects of exogenous glucocorticoids on the epidermis.
Activators of PPARs and LXR decrease the adverse effects of exogenous glucocorticoids on the epidermis.
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DOI：
10.1111/j.1600-0625.2009.00841.x
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发表时间：
2009-07
影响因子：
3.6
通讯作者：
Feingold KR
中科院分区：
文献类型：
--
作者：
Demerjian M;Choi EH;Man MQ;Chang S;Elias PM;Feingold KR
虽然糖皮质激素（GC）发挥有益作用（抗炎），但它们也对表皮具有不利作用，包括降低的表皮分化、降低的角质形成细胞增殖和降低的皮肤渗透性屏障稳态。因此，本研究的目的是开发策略，以防止这些GC毒性使用同时局部治疗氯倍他索治疗的小鼠。虽然之前已证明角质层脂质（神经酰胺、游离脂肪酸和胆固醇）的三重脂质混合物可以逆转GC诱导的皮肤屏障功能异常（Kao等人，2003年），但这种脂质混合物并不能预防GC诱导的角质形成细胞增殖或分化异常。由于PPAR α、β/δ、γ和LXR的激活剂调节角质形成细胞增殖和分化并改善渗透性屏障稳态，我们接下来评估了这些激活剂在同时GC治疗期间的作用。同时应用环格列酮（PPAR γ激活剂）、氯贝特（PPARα激活剂）或22 R（OH）胆固醇（LXR激活剂）与氯倍他索可防止外皮蛋白、聚丝蛋白和兜甲蛋白表达的降低。相比之下，PPAR β/δ激活剂（GW 501516）仅使外皮蛋白和聚丝蛋白的表达正常化，而不是兜甲蛋白。此外，局部应用PPARα、β/δ或LXR激活剂可部分防止GC处理的小鼠皮肤中角质形成细胞增殖的减少，如通过PCNA测量的，而与PPAR γ激活剂共同处理后未观察到效果。最后，在GC处理的小鼠中，PPAR γ和PPARβ/δ激活剂而不是PPAR α和LXR激活剂改善了渗透性屏障稳态。总之，这些研究表明，PPAR和LXR激活剂可以预防局部GC对表皮的几种不良影响。
While glucocorticoids (GC) exert beneficial effects (anti-inflammatory), they also have adverse effects on the epidermis including decreased epidermal differentiation, decreased keratinocyte proliferation, and decreased cutaneous permeability barrier homeostasis. Thus, the purpose of this study was to develop strategies to prevent these GC toxicities using simultaneous topical treatments in clobetasol-treated mice. While a triple-lipid mixture of stratum-corneum lipids (ceramide, free fatty acid, and cholesterol) was previously shown to reverse the GC-induced abnormality in cutaneous barrier function (Kao, et al. 2003), this lipid mixture did not prevent the GC-induced abnormalities in either keratinocyte proliferation or differentiation. Since activators of PPAR α, β/δ, γ, and LXR, regulate keratinocyte proliferation and differentiation and improve permeability barrier homeostasis, we next assessed the effects of these activators during concurrent GC treatment. Co-application of either ciglitazone (PPAR γ activator), clofibrate (PPARα activator), or 22R (OH) cholesterol (LXR activator) with clobetasol prevented the decrease in involucrin, filaggrin and loricrin expression. In contrast, a PPAR β/δ activator (GW501516) normalized only the expression of involucrin and filaggrin, but not loricrin. Moreover, topical application of PPARα, β/δ, or LXR activators partially prevented the decrease in keratinocyte proliferation in GC-treated murine skin, as measured by PCNA, while no effect was seen after co-treatment with PPAR γ activators. Finally, PPAR γ and PPARβ/δ activators but not PPAR α and LXR activators improved permeability barrier homeostasis in GC treated mice. Together, these studies demonstrate that PPAR and LXR activators can prevent several of the adverse effects of topical GC on the epidermis.
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影响因子：
3.6
作者：
Demerjian, M;Man, MQ;Feingold, KR
通讯作者：
Feingold, KR
影响因子：
6.5
作者：
Hanley, K;Ng, DC;Feingold, KR
通讯作者：
Feingold, KR
影响因子：
6.5
作者：
Jiang, Yan J.;Lu, Biao;Feingold, Kenneth R.
通讯作者：
Feingold, Kenneth R.
影响因子：
--
作者：
Ellis, CN;Varani, J;Kurtz, TW
通讯作者：
Kurtz, TW
影响因子：
6.5
作者：
LAURENCE, EB;CHRISTOPHERS, E
通讯作者：
CHRISTOPHERS, E