TNF-α–induced protein 3 is a key player in childhood asthma development and environment-mediated protection
Autor: | Sabina Illi, Anne Hyvärinen, Josef Riedler, Martin Depner, Bianca Schaub, Harald Renz, Marie-Laure Dalphin, Charlotte Braun-Fahrländer, R. Frei, Yuhan Xing, Jing Li, Monika Twardziok, Andreas Böck, P. C. Schröder, Gert Doekes, Gary W.K. Wong, Jon Genuneit, Jean-Charles Dalphin, Marjut Roponen, Anne M. Karvonen, Miranda S. Tsang, Pirkka Kirjavainen, Caroline Roduit, Jörg Kumbrink, Vincent Kaulek, Johanna Krusche, P. Pfefferle, Thomas Kirchner, Markus J. Ege, Sami Remes, Roger Lauener, Katharina Rehbach, Juha Pekkanen, Michael Kabesch, G. Loss, Amandine Divaret-Chauveau, Chun K. Wong |
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Přispěvatelé: | Department of Public Health, University of Helsinki |
Rok vydání: | 2019 |
Předmět: |
Male
0301 basic medicine Allergy DUST TNFAIP3 0302 clinical medicine Immunology and Allergy Longitudinal Studies Prospective Studies Child RISK INDUCTION IRAK1 protection 3. Good health ALLERGY A20 Child Preschool Cord blood Female environment LPS Immunology inflammatory farming Proinflammatory cytokine EARLY-LIFE 03 medical and health sciences medicine Humans EXPOSURE Tumor Necrosis Factor alpha-Induced Protein 3 childhood Asthma business.industry Infant Newborn Infant Environmental Exposure Dendritic cell medicine.disease Toll-Like Receptor 4 Cross-Sectional Studies 030104 developmental biology Gene Expression Regulation 030228 respiratory system immune development 3121 General medicine internal medicine and other clinical medicine TLR4 ENDOTOXIN business Biomarkers |
Zdroj: | Journal of Allergy and Clinical Immunology. 144:1684-1696.e12 |
ISSN: | 0091-6749 |
Popis: | Background: Childhood asthma prevalence is significantly greater in urban areas compared with rural/farm environments. Murine studies have shown that TNF-alpha-induced protein 3 (TNFAIP3; A20), an anti-inflammatory regulator of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) signaling, mediates environmentally induced asthma protection. Objective: We aimed to determine the role of TNFAIP3 for asthma development in childhood and the immunomodulatory effects of environmental factors. Methods: In a representative selection of 250 of 2168 children from 2 prospective birth cohorts and 2 cross-sectional studies, we analyzed blood cells of healthy and asthmatic children from urban and rural/farm environments from Europe and China. PBMCs were stimulated ex vivo with dust from "asthma-protective'' farms or LPS. NF-kappa B signaling-related gene and protein expression was assessed in PBMCs and multiplex gene expression assays (NanoString Technologies) in isolated dendritic cells of schoolchildren and in cord blood mononuclear cells from newborns. Results: Anti-inflammatory TNFAIP3 gene and protein expression was consistently decreased, whereas proinflammatory Toll-like receptor 4 expression was increased in urban asthmatic patients (P |
Databáze: | OpenAIRE |
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