Deficient pulmonary IFN-β expression in COPD patients
García-Valero, José (Universitat de Barcelona. Departament de Biologia Cel·lular)
Olloquequi, Jordi (Universidad Autónoma de Chile. Instituto de Ciencias Biomédicas.)
Montes, Juan F. (Universitat de Barcelona. Departament de Biologia Cel·lular)
Rodríguez, Ester. (Hospital Universitari Vall d'Hebron)
Martín-Satué, Mireia (Institut d'Investigació Biomèdica de Bellvitge)
Texidó, Laura (Universitat de Barcelona. Departament de Patologia i Terapèutica Experimental)
Ferrer Sancho, Jaume 1958- (Hospital Universitari Vall d'Hebron)
Universitat Autònoma de Barcelona

Data:	2019
Resum:	COPD patients are prone to acute infectious exacerbations that impair their quality of life and hamper prognosis. The purpose of the present study was to investigate the in situ IFN-Ǝ response in the lungs of stable COPD and non-COPD patients. Lung samples from 70 subjects (9 control never smokers, 19 control smokers without COPD, 21 patients with moderate COPD and 21 patients with very severe COPD) were studied for the expression of IFN-Ǝ, its main transcription factor, IRF-7, and two products of its autocrine function, namely RIG-I and MDA-5, by immunohistochemical techniques and quantitative real-time PCR. IFN-β, IRF-7, RIG-I and MDA-5 were widely detected in most lung cell types. In epithelial tissues and alveolar macrophages, IFN-Ǝ and IRF-7 labeling scores were decreased up to 65% and 74%, respectively, for COPD patients, paralleling an analogous reduction (43% and 65%, respectively) in the amount of their lung mRNA. Moreover, this decreased production of IFN-Ǝ in COPD patients correlated with a similar decrease in the expression of RIG-I and MDA-5, two essential members of the innate immune system. Our study indicates that most lung cells from stable COPD patients show a constitutive decreased expression of IFN-β, IRF-7, RIG-I and MDA-5, suggesting that this deficiency is the main cause of their acute viral exacerbations.
Nota:	This study was supported by the grants received by JFS from the Health Research Fund (Madrid, Spain; FIS 04/0635) and the Sociedad Española de Pneumologia (SEPAR 165 2012). None of the funders played any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank the patients who participated in this study; Dr. Joaquim Majó and Dr. María Ánge-les Montero (Anatomic Pathology Department, Vall d'Hebron University Hospital, Barcelona, Spain) for their valuable help in the histopathologic study of lung samples; Tania Martínez, for her technical support; Dr. Gloria Gannaway for her linguistic advice; and Dr. Marc Miravitlles and Dr. Joan Mª Vianney Blasi for their critical reading of the manuscript.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	DEAD Box Protein 58 ; Female ; Humans ; Interferon Regulatory Factor-7 ; Interferon-beta ; Interferon-Induced Helicase, IFIH1 ; Lung ; Male ; Middle Aged ; Pulmonary Disease, Chronic Obstructive ; Signal Transduction
Publicat a:	PloS one, Vol. 14 Núm. 6 (june 2019) , p. e0217803, ISSN 1932-6203

DOI: 10.1371/journal.pone.0217803
PMID: 31170225

16 p, 2.9 MB

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