5 277

Cited 63 times in

Protease activity enhances production of thymic stromal lymphopoietin and basophil accumulation in flaky tail mice

Authors
 Catharina S. Moniaga  ;  Se Kyoo Jeong  ;  Gyohei Egawa  ;  Saeko Nakajima  ;  Mariko Hara-Chikuma  ;  Jeong Eun Jeon  ;  Seung Hun Lee  ;  Toshihiko Hibino  ;  Yoshiki Miyachi  ;  Kenji Kabashima 
Citation
 AMERICAN JOURNAL OF PATHOLOGY, Vol.182(3) : 841-851, 2013 
Journal Title
 AMERICAN JOURNAL OF PATHOLOGY 
ISSN
 0002-9440 
Issue Date
2013
MeSH
Amino Acids/metabolism ; Animals ; Basophils/metabolism* ; Cytokines/biosynthesis* ; Dermatitis, Atopic/parasitology ; Dermatitis, Atopic/pathology ; Female ; Histidine/metabolism ; Hydrogen-Ion Concentration ; Intermediate Filament Proteins/genetics* ; Kallikreins/metabolism ; Keratinocytes/enzymology ; Keratinocytes/pathology ; Mice ; Mice, Inbred C57BL ; Mites/physiology ; Peptide Hydrolases/metabolism* ; Receptor, PAR-2/agonists ; Receptor, PAR-2/antagonists & inhibitors ; Receptor, PAR-2/metabolism ; Skin/parasitology ; Skin/pathology ; Tail
Keywords
Amino Acids/metabolism ; Animals ; Basophils/metabolism* ; Cytokines/biosynthesis* ; Dermatitis, Atopic/parasitology ; Dermatitis, Atopic/pathology ; Female ; Histidine/metabolism ; Hydrogen-Ion Concentration ; Intermediate Filament Proteins/genetics* ; Kallikreins/metabolism ; Keratinocytes/enzymology ; Keratinocytes/pathology ; Mice ; Mice, Inbred C57BL ; Mites/physiology ; Peptide Hydrolases/metabolism* ; Receptor, PAR-2/agonists ; Receptor, PAR-2/antagonists & inhibitors ; Receptor, PAR-2/metabolism ; Skin/parasitology ; Skin/pathology ; Tail
Abstract
Epidermal barrier abnormality due to filaggrin deficiency is an important predisposing factor in the development of atopic dermatitis (AD). In addition, the expression of thymic stromal lymphopoietin (TSLP) in keratinocytes (KCs), induced by barrier disruption, can promote type 2 helper T-cell polarization. Protease activity, including protease-activated receptor-2 (PAR-2), is also known to be involved in epidermal barrier function in AD. However, to our knowledge, the relationship between protease activity and filaggrin deficiency from the perspective of AD has not been elucidated. Flaky tail (Flg(ft)) mice, known to have a mutation in the filaggrin gene, were used to assess the role of protease in KCs in the steady state and the mite-induced AD-like skin inflammation model. In the steady state, the expression and activity levels of endogenous proteases, kallikreins 5, 7, and 14, in the skin and TSLP were higher in Flg(ft) than in control mice. In addition, activation of PAR-2 by its agonist induced the production of TSLP in KCs of Flg(ft) mice, which was abrogated by a newly developed PAR-2 antagonist. Application of the PAR-2 antagonist improved symptoms and basophil accumulation in Flg(ft) mice treated with mite extracts. These results suggest that possibly through the PAR-2 activation in KCs, filaggrin deficiency induces TSLP production and basophil accumulation, which play important roles in the establishment of AD.
Full Text
http://www.sciencedirect.com/science/article/pii/S0002944013000072
DOI
10.1016/j.ajpath.2012.11.039
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Lee, Seung Hun(이승헌)
Jeon, Jeong Eun(전정은)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/87707
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links