Nucleotide-Oligomerizing Domain-1 Activation Exaggerates Cigarette Smoke-Induced Chronic Obstructive Pulmonary-Like Disease in Mice

• Main Authors: Han G, Li M, Du J, Chen Y, Xu C
• Format: Article
• Language: English
• Published: Dove Medical Press 2021-09-01
• Series: International Journal of COPD
• Subjects: copd; pulmonary damage; inflammation; nod1; tlr4/nf-κb signaling
• Online Access: https://www.dovepress.com/nucleotide-oligomerizing-domain-1-activation-exaggerates-cigarette-smo-peer-reviewed-fulltext-article-COPD

Guangchao Han, Min Li, Junfeng Du, Yang Chen, Chen Xu Department of Respiratory and Critical Care Medicine, Cangzhou Central Hospital, Cangzhou, 061000, Hebei, People’s Republic of ChinaCorrespondence: Guangchao HanDepartment of Respiratory and Critical Care Medicine, Cangzhou Central Hospital, No. 16 Xinhua West Road, Cangzhou, 061000, Hebei, People’s Republic of ChinaTel [phone]Email [e-mail]: Chronic obstructive pulmonary disease (COPD) is a progressive condition related to abnormal inflammatory responses. As an inflammatory driver, nucleotide-binding oligomerizing domain-1 (NOD1) is highly expressed in pulmonary inflammatory cells; however, the roles of NOD1 in COPD are unknown.Methods: A COPD mouse model was established by lipopolysaccharides tracheal instillation plus cigarette smoke (CS) exposure. NOD1 activation was induced by C12-iE-DAP (iE) treatment in both control and COPD mice. Inflammatory infiltration, pulmonary histological damage and gene expression were measured to evaluate the lung function of treated mice.Results: The results showed that NOD1 was up-regulated in COPD mice, which significantly exaggerated CS-induced impairment of lung function, demonstrated by increased airway resistance, functional residual capacity and pulmonary damages. Mechanistically, NOD1 activation strongly activated the TLR4/NF-κB signaling pathway and then increased inflammatory responses and promoted the secretion of inflammatory cytokines.Discussion: This study demonstrates that NOD1 is an important risk factor in the progression of COPD; therefore, targeting NOD1 in lung tissues is a potential strategy for COPD treatment.Keywords: COPD, pulmonary damage, inflammation, NOD1, TLR4/NF-κB signaling