School of Life Science and Biotechnology, College of Natural Sciences, Kyungpook National University, Buk-ku, Daegu, Republic of Korea.
J Invest Dermatol. 2012 Apr;132(4):1169-76. doi: 10.1038/jid.2011.404. Epub 2011 Dec 15.
Atopic dermatitis (AD) is a chronically relapsing, non contagious pruritic skin disease with two phases: acute and chronic. Cysteine protease cathepsin S (CTSS) is involved in inflammatory processes, possibly leading to atherosclerosis and asthma. Recently, it has been reported that CTSS can arouse a predominant sensation of itch accompanied by classical ligand–receptor signaling [corrected]. 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.
特应性皮炎（AD）是一种慢性复发性、非传染性瘙痒性皮肤病，有两个阶段：急性和慢性。半胱氨酸蛋白酶组织蛋白酶 S（CTSS）参与炎症过程，可能导致动脉粥样硬化和哮喘。最近，有报道称 CTSS 可以引起瘙痒的主要感觉，同时伴有经典的配体-受体信号转导[已更正]。最近，CTSS 被证明是蛋白酶激活受体-2（PAR-2）的配体，PAR-2 与瘙痒有关。在这项研究中，我们表明 CTSS 过表达转基因（TG）小鼠自发地发展出类似于慢性 AD 的皮肤疾病。这项研究的结果表明，CTSS 过表达触发树突状细胞（DC）中 PAR-2 的表达，从而促进 CD4+分化，这涉及主要组织相容性复合物（MHC）II 类的表达。此外，我们研究了肥大细胞和巨噬细胞，发现 CTSS 过表达 TG 小鼠中 Th1 细胞相关细胞因子的平均水平明显高于 Th2 细胞相关细胞因子。这些结果表明，由于 CTSS 过表达导致 DC 中 PAR-2 表达增加，诱导搔抓行为和 Th1 细胞相关细胞因子表达，并可能引发慢性 AD 症状。
