Human cystatin SN is an endogenous protease inhibitor that prevents allergic rhinitis

The Journal of Allergy and Clinical Immunology
Ayumi FukuokaTomohiro Yoshimoto

Abstract

Protease allergens disrupt epithelial barriers to exert their allergenicity. Cystatin SN (encoded by CST1) is an endogenous cysteine protease inhibitor upregulated in nasal epithelia in patients with allergic rhinitis (AR). We sought to investigate the protective effect of human cystatin SN on AR symptoms using pollen-induced AR mouse models. We performed an in vitro protease activity assay to evaluate the effect of recombinant human cystatin SN (rhCystatin SN) on Japanese cedar (JC) or ragweed proteases. A human nasal epithelial cell line, RPMI 2650, was used to examine tight junction (TJ) disruption in vitro. Mice were sensitized and nasally challenged with JC or ragweed pollens with or without rhCystatin SN to examine the effect of rhCystatin SN on AR symptoms and the epithelial barrier in vivo. Because mice lack CST1, we generated transgenic (Tg) mice expressing human CST1 under control of its genomic control region (hCST1-Tg mice) to examine the role of cystatin SN in physiologically expressed conditions. rhCystatin SN inhibited JC but not ragweed protease activities and prevented JC-induced but not ragweed-induced TJ disruption in vitro. Exogenous administration of rhCystatin SN ameliorated JC-induced but not ragweed-indu...Continue Reading

Citations

Jan 29, 2020·Expert Review of Clinical Immunology·Chengshuo WangLuo Zhang
Dec 4, 2019·Clinical and Translational Science·Kai XueZonggui Wang
Apr 16, 2020·Frontiers in Cell and Developmental Biology·Anu Laulajainen-HongistoRobert Kern
Nov 13, 2020·International Journal of Food Sciences and Nutrition·Nicole M Delimont, Sarah Nickel
Apr 27, 2021·ERJ Open Research·Ulrika KäckJon R Konradsen
Nov 23, 2021·Cancer Investigation·Barghavi VMaddaly Ravi

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