Chemokine receptor 1 pathway mediagtes the progression of airway inflammation in a smoking-induced chronic obstructive pulmonary disease mouse model

Abstract

To investigate the role of chemokine receptor 1 (CCR1) and mechanisms underlying airway inflammation in smoking-related chronic obstructive pulmonary disease (COPD), we established a mouse model of smoking-induced COPD. Pathological changes in the bronchial mucosa were assessed using hematoxylin and eosin staining, CCR1 expression and cell apoptosis were detected via immunofluorescence and TUNEL, and the expression of the CCR1 downstream pathway was detected via real-time quantitative PCR and western blotting. The expression of the chemokine MIP-1β and the inflammatory factors IL-6 and TNF-α in bronchoalveolar lavage fluid was detected using enzyme-linked immunosorbent assays. The bronchial mucosa of the COPD model mice transfected with the vector showed apoptosis, inflammatory cell infiltration, airway remodeling, and emphysema. Furthermore, the COPD model mice exhibited significantly increased CCR1 signaling and chemokine concentrations, which were further aggravated by overexpressed-CCR1 lentiviral transfection but inhibited by shRNA-CCR1 lentiviral transfection or BX471 pretreatment. These results, combined with our previous findings, elucidate the role of and mechanisms underlying CCR1 signaling in the progression of COPD, both in vivo and in vitro. This study has the potential to provide theoretical evidence for the diagnosis and therapeutic strategies of cigarette smoke-induced inflammation in COPD patients.