Effect and mechanism of chemokine receptor 1 in airway inflammation in a mouse model of chronic obstructive pulmonary disease
Year: 2025
Type: article
Abstract: Objective We aimed to investigate the role and mechanisms of chemokine receptor 1 (CCR1) in airway inflammation in chronic obstructive pulmonary disease (COPD) mice.Methods We established a mouse model of cigarette smoke-induced COPD. A mouse model with CCR1 overexpression or silencing COPD was established by tail vein injection of CCR1 overexpression lentivirus or shRNA-CCR1 lentivirus. Pathological changes in the bronchial mucosa were assessed using hematoxylin and eosin (HE) staining. CCR1 expression and cell apoptosis were detected via immunofluorescence and TUNEL. The levels of chemokine (MIP-1β) and inflammatory factors (IL-6 and TNF-α) in bronchoalveolar lavage fluid were detected using enzyme-linked immunosorbent assay (ELISA). The expression levels of the factors in the CCR1 downstream pathway were detected via RT-qPCR and western blotting.Results Compared with the COPD mice, the bronchial mucosa of the COPD model mice transfected with the vector showed apoptosis, inflammatory cell infiltration, airway remodeling, and emphysema. The COPD model mice exhibited significantly increased expression levels of p-IKK, p-JAK2, STAT3, and p-p65 and chemokine concentrations (MIP-1β, IL-6 and TNF-α) than the control mice (p < 0.05), which were further aggravated by overexpressed-CCR1 lentiviral transfection but inhibited by shRNA-CCR1 lentiviral transfection or BX471 pretreatment (p < 0.05).Conclusion CCR1 aggravates the progression of COPD mice by activating JAK/STAT3/NF-κB signaling. This study has the potential to provide theoretical evidence for the diagnosis and therapeutic strategies of cigarette smoke-induced inflammation in COPD patients.
Source: Experimental Lung Research
Authors: Wei Wei, Suzhen Ju, Yanfang Yu, Zhen Wang, Kaishun Zhao
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4417093709