Overexpression of Cathepsin S Induces Chronic Atopic Dermatitis in Mice
Overexpression of Cathepsin S Induces Chronic Atopic Dermatitis in Mice
复制标题
DOI：
10.1038/jid.2011.404
复制
发表时间：
2012-04-01
影响因子：
6.5
通讯作者：
Ryoo, Zae Young
中科院分区：
文献类型：
--
作者：
Kim, Nari;Bae, Ki Beom;Ryoo, Zae Young
特应性皮炎（AD）是一种慢性复发性、非接触性皮炎性皮肤病，分为急性期和慢性期。先前的研究表明，半胱氨酸蛋白酶组织蛋白酶S（CTSS）与炎症过程有关，包括动脉粥样硬化和哮喘。这种或其他半胱氨酸蛋白酶可能引起瘙痒或成为经典配体-受体信号级联的一部分的可能性以前没有被考虑过。最近，CTSS被证明是蛋白酶激活受体-2（PAR-2）的配体，与瘙痒相关。在这项研究中，我们表明CTSS过表达转基因（TG）小鼠自发地发展一种类似于慢性AD的皮肤疾病。本研究的结果表明，CTSS过表达触发PAR-2在树突状细胞（DC）的表达，导致促进CD 4（+）分化，这是参与主要组织相容性复合物（MHC）II类表达。此外，我们研究了肥大细胞和巨噬细胞，发现CTSS过表达的TG小鼠中1型T辅助细胞（Th 1）相关细胞因子的平均水平显著高于2型T辅助细胞（Th 2）相关细胞因子。这些结果表明，增加PAR-2的表达在DC中作为CTSS过表达的结果诱导抓挠行为和Th 1细胞相关的细胞因子的表达，并可以触发慢性AD症状。
Atopic dermatitis (AD) is a chronically relapsing, noncontagious pruritic skin disease with two phases: acute and chronic. Previous studies have shown that the cysteine protease cathepsin S (CTSS) is linked to inflammatory processes, including atherosclerosis and asthma. The possibility that this or other cysteine proteases might cause itching or be part of a classical ligand-receptor signaling cascade has not been previously considered. Recently, CTSS was shown to be a ligand for proteinase-activated receptor-2 (PAR-2), which is associated with itching. In this study, we show that CTSS-overexpressing transgenic (TG) mice spontaneously develop a skin disorder similar to chronic AD. The results of this study suggest that CTSS overexpression triggers PAR-2 expression in dendritic cells (DCs), resulting in the promotion of CD4(+) differentiation, which is involved in major histocompatibility complex (MHC) class II expression. In addition, we investigated mast cells and macrophages and found significantly higher mean levels of T helper type 1 (Th1) cell-associated cytokines than T helper type 2 (Th2) cell-associated cytokines in CTSS-overexpressing TG mice. These results suggest that increased PAR-2 expression in DCs as a result of CTSS overexpression induces scratching behavior and Th1 cell-associated cytokine expression, and can trigger chronic AD symptoms.