A Alase1, J Seltmann, T Werfel, M Wittmann. 1. Leeds Institute of Molecular Medicine, Division of Rheumatic and Musculoskeletal Disease, LMBRU, University of Leeds, Leeds, UK. a.a.alase@leeds.ac.uk
Abstract
BACKGROUND: Interleukin (IL)-33 is a member of the IL-1 family and has been implicated in Th2-driven allergic diseases such as atopic dermatitis (AD) and asthma. The principal Th2 cytokine IL-4, found highly expressed in acute allergic eczema, is known to downregulate human β-defensin 2 (hBD2) expression in human keratinocytes and this is associated with superinfection in patients with AD. OBJECTIVES: To investigate the effect of IL-33 on the expression of hBD2 in human keratinocytes. METHODS: hBD2 production by stimulated keratinocytes was measured by enzyme-linked immunosorbent assay. RESULTS: Our results showed that serum is a very potent inducer of hBD2 and 2·5% human serum was much more potent in inducing hBD2 than 20 ng mL(-1) of tumour necrosis factor-α. Interestingly, serum from patients with AD showed an impaired ability to induce hBD2 in normal keratinocytes. IL-33 significantly downregulated serum-induced hBD2. The downregulatory capacity of IL-33 was found to be 1·5- to 2-fold weaker compared with IL-4. CONCLUSIONS: Our data suggest that IL-33 can significantly contribute to the decreased expression of hBD2 in acute eczematous reaction clinically characterized by spongiosis and oozing - thus indicative for contact of the epidermis with serum components.
BACKGROUND:Interleukin (IL)-33 is a member of the IL-1 family and has been implicated in Th2-driven allergic diseases such as atopic dermatitis (AD) and asthma. The principal Th2 cytokine IL-4, found highly expressed in acute allergic eczema, is known to downregulate human β-defensin 2 (hBD2) expression in human keratinocytes and this is associated with superinfection in patients with AD. OBJECTIVES: To investigate the effect of IL-33 on the expression of hBD2 in human keratinocytes. METHODS:hBD2 production by stimulated keratinocytes was measured by enzyme-linked immunosorbent assay. RESULTS: Our results showed that serum is a very potent inducer of hBD2 and 2·5% human serum was much more potent in inducing hBD2 than 20 ng mL(-1) of tumour necrosis factor-α. Interestingly, serum from patients with AD showed an impaired ability to induce hBD2 in normal keratinocytes. IL-33 significantly downregulated serum-induced hBD2. The downregulatory capacity of IL-33 was found to be 1·5- to 2-fold weaker compared with IL-4. CONCLUSIONS: Our data suggest that IL-33 can significantly contribute to the decreased expression of hBD2 in acute eczematous reaction clinically characterized by spongiosis and oozing - thus indicative for contact of the epidermis with serum components.
Authors: Daniel Aguilar; Mariona Pinart; Gerard H Koppelman; Yvan Saeys; Martijn C Nawijn; Dirkje S Postma; Mübeccel Akdis; Charles Auffray; Stéphane Ballereau; Marta Benet; Judith García-Aymerich; Juan Ramón González; Stefano Guerra; Thomas Keil; Manolis Kogevinas; Bart Lambrecht; Nathanael Lemonnier; Erik Melen; Jordi Sunyer; Rudolf Valenta; Sergi Valverde; Magnus Wickman; Jean Bousquet; Baldo Oliva; Josep M Antó Journal: PLoS One Date: 2017-06-09 Impact factor: 3.240
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