TY - JOUR
T1 - Imprinting of bronchial epithelial cells upon in vivo rhinovirus infection in people with asthma
AU - Ravi, Abilash
AU - Chowdhury, Saheli
AU - Dijkhuis, Annemiek
AU - Dierdorp, Barbara S.
AU - Dekker, Tamara
AU - Kruize, Rianne
AU - Piñeros, Yanaika S. Sabogal
AU - Majoor, Christof J.
AU - Sterk, Peter J.
AU - Lutter, René
N1 - Funding Information: Support statement: This study was supported by the Netherlands Asthma Foundation (currently Lung Foundation; projects 3.2.10.069, 3.2.07.012 and 3.2.06.031) and GSK (CRT 114696). Funding information for this article has been deposited with the Crossref Funder Registry. Funding Information: Conflict of interest: A. Ravi has nothing to disclose. S. Chowdhury has nothing to disclose. A. Dijkhuis has nothing to disclose. B.S. Dierdorp has nothing to disclose. T. Dekker has nothing to disclose. R. Kruize has nothing to disclose. Y.S. Sabogal Piñeros has nothing to disclose. C.J. Majoor has nothing to disclose. P.J. Sterk has nothing to disclose. R. Lutter reports support for the present manuscript from the Netherlands Asthma Foundation (now Netherlands Lung Foundation; grant numbers 3-2-07-012 and 3.2.10.069) and GlaxoSmithKline (CRT 114696). Publisher Copyright: © The authors 2022.
PY - 2022/4/1
Y1 - 2022/4/1
N2 - Background Defective translocation of the translational repressor TIAR (T-cell internal antigen receptor) in bronchial epithelial cells (BECs) from asthma patients underlies epithelial hyperresponsiveness, reflected by an exaggerated production of a select panel of inflammatory cytokines such as CXCL-8, interleukin (IL)-6, granulocyte colony-stimulating factor, CXCL-10, upon exposure to tumour necrosis factor (TNF) and IL-17A. With this study we aimed to clarify whether epithelial hyperresponsiveness is a consistent finding, is changed upon in vivo exposure to rhinovirus (RV)-A16 and applies to the bronchoconstrictor endothelin-1. Methods BECs were obtained from asthma patients (n=18) and healthy individuals (n=11), 1 day before and 6 days post-RV-A16 exposure. BECs were cultured and stimulated with TNF and IL-17A and inflammatory mediators were analysed. The bronchoalveolar lavage fluid (BALF) was obtained in parallel with BECs to correlate differential cell counts and inflammatory mediators with epithelial hyperresponsiveness. Results Epithelial hyperresponsiveness was confirmed in sequential samples and even increased in BECs from asthma patients after RV-A16 exposure, but not in BECs from healthy individuals. Endothelin-1 tended to increase in BECs from asthma patients collected after RV-A16 exposure, but not in BECs from healthy individuals. In vitro CXCL-8 and endothelin-1 production correlated. In vivo relevance for in vitro CXCL-8 and endothelin-1 production was shown by correlations with forced expiratory volume in 1 s % predicted and CXCL-8 BALF levels. Conclusion Epithelial hyperresponsiveness is an intrinsic defect in BECs from asthma patients, which increases upon viral exposure, but not in BECs from healthy individuals. This epithelial hyperresponsiveness also applies to the bronchoconstrictor endothelin-1, which could be involved in airway obstruction.
AB - Background Defective translocation of the translational repressor TIAR (T-cell internal antigen receptor) in bronchial epithelial cells (BECs) from asthma patients underlies epithelial hyperresponsiveness, reflected by an exaggerated production of a select panel of inflammatory cytokines such as CXCL-8, interleukin (IL)-6, granulocyte colony-stimulating factor, CXCL-10, upon exposure to tumour necrosis factor (TNF) and IL-17A. With this study we aimed to clarify whether epithelial hyperresponsiveness is a consistent finding, is changed upon in vivo exposure to rhinovirus (RV)-A16 and applies to the bronchoconstrictor endothelin-1. Methods BECs were obtained from asthma patients (n=18) and healthy individuals (n=11), 1 day before and 6 days post-RV-A16 exposure. BECs were cultured and stimulated with TNF and IL-17A and inflammatory mediators were analysed. The bronchoalveolar lavage fluid (BALF) was obtained in parallel with BECs to correlate differential cell counts and inflammatory mediators with epithelial hyperresponsiveness. Results Epithelial hyperresponsiveness was confirmed in sequential samples and even increased in BECs from asthma patients after RV-A16 exposure, but not in BECs from healthy individuals. Endothelin-1 tended to increase in BECs from asthma patients collected after RV-A16 exposure, but not in BECs from healthy individuals. In vitro CXCL-8 and endothelin-1 production correlated. In vivo relevance for in vitro CXCL-8 and endothelin-1 production was shown by correlations with forced expiratory volume in 1 s % predicted and CXCL-8 BALF levels. Conclusion Epithelial hyperresponsiveness is an intrinsic defect in BECs from asthma patients, which increases upon viral exposure, but not in BECs from healthy individuals. This epithelial hyperresponsiveness also applies to the bronchoconstrictor endothelin-1, which could be involved in airway obstruction.
UR - http://www.scopus.com/inward/record.url?scp=85130767705&partnerID=8YFLogxK
U2 - https://doi.org/10.1183/23120541.00522-2021
DO - https://doi.org/10.1183/23120541.00522-2021
M3 - Article
C2 - 35449758
SN - 2312-0541
VL - 8
JO - ERJ open research
JF - ERJ open research
IS - 2
M1 - 00522-2021
ER -