Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6078124 | Journal of Investigative Dermatology | 2012 | 9 Pages |
Abstract
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.
Related Topics
Health Sciences
Medicine and Dentistry
Dermatology
Authors
Nari Kim, Ki Beom Bae, Myoung Ok Kim, Dong Hoon Yu, Hei Jung Kim, Hyung Soo Yuh, Young Rae Ji, Si Jun Park, Sol Kim, Kyu-Hee Son, Sang-Joon Park, Duhak Yoon, Dong-Seok Lee, Sanggyu Lee, Hyun-Shik Lee, Tae-Yoon Kim, Zae Young Ryoo,