Impaired lnc-IL7R modulatory mechanism of Toll-like receptors is associated with an exacerbator phenotype of chronic obstructive pulmonary disease.
FASEB J
; 34(10): 13317-13332, 2020 10.
Article
en En
| MEDLINE
| ID: mdl-32780913
ABSTRACT
Patients with chronic obstructive pulmonary disease (COPD) are susceptible to bacterial infections, which worsen lung inflammation and contribute to lung function decline and acute exacerbation. Long noncoding (lnc) RNAs are emerging regulators of inflammation with unknown clinical relevance. Herein, we report that levels of the Toll-like receptor (TLR)-related lnc interleukin (IL) 7 receptor (IL7R) were significantly reduced in peripheral blood mononuclear cells from patients with COPD compared with those from normal controls, and the levels were correlated with pulmonary function. Moreover lnc-IL7R levels were reduced in lavaged alveolar macrophages and primary human small airway epithelial cells (HSAEpCs) from patients with COPD. Lnc-IL7R knockdown in primary human macrophages, HSAEpCs, and human pulmonary microvascular endothelial cells (HPMECs) significantly augmented the induction of proinflammatory mediators after TLR2/4 activation. By contrast, lnc-IL7R overexpression attenuated inflammation after TLR2/4 activation. Similar results with lnc-IL7R-mediated inflammation were observed in COPD HSAEpCs. Mechanistically, lnc-IL7R mediated a repressive chromatin state of the proinflammatory gene promoter as a result of decreased acetylation (H3K9ac) and increased methylation (H3K9me3 and H3K27me3). Plasma lnc-IL7R levels were reduced in patients with COPD who experienced more acute exacerbation in the previous year. Notably, patients with lower lnc-IL7R levels in the subsequent year had increased exacerbation risk. Low lnc-IL7R expression in COPD may augment TLR2/4-mediated inflammation and be associated with acute exacerbation.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fenotipo
/
Enfermedad Pulmonar Obstructiva Crónica
/
Receptores Toll-Like
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Subunidad alfa del Receptor de Interleucina-7
/
ARN Largo no Codificante
Tipo de estudio:
Risk_factors_studies
Límite:
Aged
/
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
FASEB J
Asunto de la revista:
BIOLOGIA
/
FISIOLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Taiwán