Hendriks A G M, Keijsers R R M C, Seyger M M B, van de Kerkhof P C M, van Erp P E J
Department of Dermatology, Radboud university medical center, Nijmegen, The Netherlands.
Skin Pharmacol Physiol. 2014;27(3):120-6. doi: 10.1159/000354119. Epub 2014 Jan 4.
Research has revealed new insights into the pathogenesis of psoriasis, leading to new therapeutic options. So far the order of changes in the pathogenesis of psoriasis is unclear. The responses to cutaneous leukotriene B4 (LTB4) application have been studied in the past as an in vivo model for inflammation. The aim of the present study is to find out the order of changes of key steps in inflammation, which all have been shown to be involved in mature psoriatic lesions.
To study the dynamics of the consecutive stages of inflammation in challenged skin as a reflection of a psoriasis-like inflammatory response.
We examined the dynamics of epidermal growth control and the key representatives of the innate and acquired immune system during the first 72 h after challenging the skin by LTB4 application.
Interleukin 17-positive (IL-17+) cells dominate the acute phase of inflammation, whereas T-Bet+ cells seem to increase gradually during the entire observation period. This indicates a more important role for IL-17 in the unstable phase of inflammation and a more prominent role for T-Bet+ cells within the chronic phase.
The present model is highly reproducible and is useful in studying the dynamics of a psoriasis-like inflammation with respect to key components of immunity. It could provide a useful tool to study the immediate biological effects of new therapies like anti-IL-17 drugs on IL-17 production and effects on cutaneous inflammation and epidermal proliferation in vivo.
研究揭示了银屑病发病机制的新见解,从而带来了新的治疗选择。到目前为止,银屑病发病机制中变化的顺序尚不清楚。过去曾研究过皮肤应用白三烯B4(LTB4)后的反应,将其作为炎症的体内模型。本研究的目的是找出炎症关键步骤的变化顺序,这些步骤均已被证明与成熟银屑病皮损有关。
研究受刺激皮肤中炎症连续阶段的动态变化,以反映银屑病样炎症反应。
在应用LTB4刺激皮肤后的最初72小时内,我们检测了表皮生长调控以及先天性和获得性免疫系统的关键代表的动态变化。
白细胞介素17阳性(IL-17+)细胞在炎症急性期占主导,而T-Bet+细胞在整个观察期似乎逐渐增加。这表明IL-17在炎症不稳定期发挥更重要的作用,而T-Bet+细胞在慢性期发挥更突出的作用。
本模型具有高度可重复性,可用于研究银屑病样炎症在免疫关键成分方面的动态变化。它可为研究抗IL-17药物等新疗法对IL-17产生的直接生物学效应以及对体内皮肤炎症和表皮增殖的影响提供有用的工具。