VGX-1027 inhibits PM2.5-induced lung inflammation and airway hyperresponsiveness in mice / 中国药理学通报

ABSTRACT

Aim: To investigate whether VGX-1027 could prevent PM2.5-induced mouse lung inflammation and airway hyperresponsiveness. Methods: Fortyeight C57BL/6 mice were randomly divided into control group, VGX-1027(50 mg · kg-1) + PBS group, PM2.5 group, VGX-1027 (12. 5 mg · kg-1) + PM2.5 group, VGX-1027(25 mg · kg-1) + PM2.5 group, and VGX-1027(50 mg · kg-1) + PM2.5 group. Mice were injected intraperitoneally with PBS or corresponding doses of VGX-1027 one hour before intranasal instillation of PBS or PM2.5(7. 8 mg · kg-1) for two consecutive days. 24 hours after last intranasal instillation, airway hyperresponsiveness and bronchoalveolar lavage fluid (BALF) cell numbers were measured. Lung inflammation scores were evaluated by HE staining and the levels of inflammatory cytokines in BALF were detected by ELISA, and the expressed levels of NLRP3 and caspase-1, as well as the phosphorylation levels of NF-kB protein were determined using Western blotting. Results: PM2.5 intranasal instillation induced significant lung inflammation and airway hyperresponsiveness. In the PM2.5 group, VGX-1027 at 12. 5 mg · kg-1 did not inhibit PM2.5-induced airway hyperresponsiveness and lung inflammatory infiltration compared to PM2.5-instilled mice; however, VGX-1027 at 25 and 50 mg · kg-1 inhibited PM2.5-induced airway hyperresponsiveness and lung inflammatory infiltration, decreased the number of inflammatory cells and the levels of inflammatory factors in BALF, and down-regulated NLRP3 and caspase-1 expression, as well as the phosphorylation levels of NF-κB. Conclusion: VGX-1027 could inhibit PM2.5-induced lung inflammation and airway hyperresponsiveness in mice.