Abstract
Objective: The formyl peptide receptor-1 (FPR-1) has been reported to be implicated in the regulation of inflammatory disorders, while its role in cigarette smoke (CS)–induced airway inflammation has not been fully explained. In this study, we investigated the role of FPR-1 in CS-induced airway inflammation and the possible mechanism through gene knockout (KO) technology and transcriptional study. Methods: FPR-1 KO or wild-type C57BL/6 mice were exposed to mainstream CS to establish an airway inflammation model. Cell counts and pro-inflammatory cytokines were measured in bronchoalveolar lavage fluid (BALF). Lung tissues were collected for histological examination, polymerase chain reaction, Western blot, transcriptomic gene study, and related bioinformatics analysis. Results: CS exposure induced significant histological inflammatory changes, increased neutrophils, and pro-inflammatory cytokines in the BALF of wild-type mice, which were all attenuated by KO of FPR-1. The transcriptomic gene study showed a total of 198 up-regulated genes and 282 down-regulated genes in mouse lungs. Bioinformatics analysis including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) suggested these differentiated expressed genes were significantly related to the immune, chemotaxis responses, and cross-talked with a complicated network of signaling pathways including NF-κB. Western blot validated that KO of FPR-1 inhibited CS-induced NF-κB activation. Conclusion: Knockout of FPR-1 significantly ameliorates CS-induced airway inflammation in mice, possibly via its related immune-chemotaxis responses and inhibition of NF-κB activation.
Highlights
Chronic obstructive pulmonary disease (COPD) is characterized by persistent respiratory symptoms, airflow limitation, and chronic airway inflammation (Wang et al, 2018), and it was estimated that there are 99.9 million people with COPD in China based on the latest epidemiological studies (Wang et al, 2018)
cigarette smoke (CS) exposure induced significant histological inflammatory changes, increased neutrophils, and pro-inflammatory cytokines in the bronchoalveolar lavage fluid (BALF) of wild-type mice, which were all attenuated by KO of formyl peptide receptors (FPRs)-1
Bioinformatics analysis including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) suggested these differentiated expressed genes were significantly related to the immune, chemotaxis responses, and cross-talked with a complicated network of signaling pathways including NF-κB
Summary
Chronic obstructive pulmonary disease (COPD) is characterized by persistent respiratory symptoms, airflow limitation, and chronic airway inflammation (Wang et al, 2018), and it was estimated that there are 99.9 million people with COPD in China based on the latest epidemiological studies (Wang et al, 2018). Severe decrease in the number and function of peripheral T cells did not influence the development of pulmonary changes induced by CS in mice (De Cunto et al, 2016) and lung inflammation still persisted after smoking cessation in mice (De Cunto et al, 2018) It suggested that innate immunity is a leading actor in the early and late development of pulmonary changes in COPD. FPR-1 has been reported to play a role in CS-induced lung emphysema in mice (Cardini et al, 2012), ongoing lung inflammation, and progression of COPD in mice (De Cunto et al, 2018) These studies confirmed the role of FPR-1 in the regulation of inflammation, and therapy targeted on FPR-1 may provide a novel direction for inflammatory lung diseases. The current study aimed to investigate the effects and molecular mechanisms of FPR-1 in CS-induced airway inflammation through the gene knockout (KO) animal study, transcriptomic study, and followed by bioinformatics analysis
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