Inhibitory Effect of P22077 on Airway Inflammation in Rats with COPD and Its Mechanism

Abstract

Di Zeng,1,* Wenbo Zhang,2,* Xiaoju Chen,3 Guochun Ou,4 Yuewei Huang,2 Chengxiu Yu2 1Department of General Practice, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, People’s Republic of China; 3Clinical Medical College, Affiliated Hospital of Chengdu University, Chengdu, Sichuan, 610081, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, Suining Central Hospital, Suining, Sichuan, 629000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoju Chen, Clinical Medical College, Affiliated Hospital of Chengdu University, Chengdu, Sichuan, 610081, People’s Republic of China, Email [email protected]: Here, we studied the pharmacological effect of P22077 on airway inflammation induced by lipopolysaccharide and cigarette smoke and explored the therapeutic mechanism of P22077 in COPD model RAT.Patients and Methods: The COPD model was established by lipopolysaccharide combined with fumigation; animals were treated with vehicle or P22077. Serum, bronchoalveolar lavage fluid (BALF), and lung tissues were collected for analysis.Results: Our results showed that P22077 treatment significantly improved the airway inflammation of COPD model RAT and reduced the recruitment of leukocytes in BALF, and hypersecretion of interleukin-18 (IL-18), interleukin-1β (IL-1β) in BALF and serum. H&E staining showed that P22077 treatment could effectively reduce emphysema, immune cell infiltration and airway wall destruction. PAS staining showed that The proliferation of cup cells in the airway wall and the number of bronchial cup cells were significantly reduced in rats treated with P22077. In addition, we found that P22077 treatment suppressed the generation of the NLRP3/ASC/Caspase 1 inflammasome complex to inhibit the inflammatory response caused by IL-1β and IL-18.Conclusion: Conclusion: P22077 inhibits expression of NLRP3 pathway-related inflammatory factors and proteins and reduces the airway inflammatory response and inflammatory cell aggregation in COPD rats. The underlying mechanism may be related to the down-regulation of NLRP3 inflammatory vesicle signaling pathway expression.Keywords: COPD, ubiquitinase inhibitors, P22077, airway inflammation, NLRP3

Keywords

• copd
• ubiquitinase inhibitors
• p22077
• airway inflammation
• nlrp3.