title: Overexpression of cathepsin S induces chronic atopic dermatitis in mice.
abstract: 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.
authors.affiliation: School of Life Science and Biotechnology, College of Natural Sciences, Kyungpook National University, Buk-ku, Daegu, Republic of Korea.
authors.forename: Nari
authors.initials: N
authors.lastname: Kim
authors.forename: Ki Beom
authors.initials: KB
authors.lastname: Bae
authors.forename: Myoung Ok
authors.initials: MO
authors.lastname: Kim
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Yu
authors.forename: Hei Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Hyung Soo
authors.initials: HS
authors.lastname: Yuh
authors.forename: Young Rae
authors.initials: YR
authors.lastname: Ji
authors.forename: Si Jun
authors.initials: SJ
authors.lastname: Park
authors.forename: Sol
authors.initials: S
authors.lastname: Kim
authors.forename: Kyu-Hee
authors.initials: KH
authors.lastname: Son
authors.forename: Sang-Joon
authors.initials: SJ
authors.lastname: Park
authors.forename: Duhak
authors.initials: D
authors.lastname: Yoon
authors.forename: Dong-Seok
authors.initials: DS
authors.lastname: Lee
authors.forename: Sanggyu
authors.initials: S
authors.lastname: Lee
authors.forename: Hyun-Shik
authors.initials: HS
authors.lastname: Lee
authors.forename: Tae-Yoon
authors.initials: TY
authors.lastname: Kim
authors.forename: Zae Young
authors.initials: ZY
authors.lastname: Ryoo
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D002403:Cathepsins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D002908:Chronic Disease; D003713:Dendritic Cells / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D008407:Mast Cells / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D044464:Receptor, PAR-2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D015854:Up-Regulation
chemical_list: D044464:Receptor, PAR-2; D002403:Cathepsins; C028217:cathepsin S