Drug Design, Development and Therapy (May 2020)
The NK-1R Antagonist Aprepitant Prevents LPS-Induced Oxidative Stress and Inflammation in RAW264.7 Macrophages
Abstract
Xiao-nan Zhao,* Zhen-zi Bai,* Cheng-hua Li, Chuan-lun Sheng, Hong-yan Li Department of Infectious, The Third Hospital of Jilin University, Changchun City, Jilin Province 130033, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hong-yan LiDepartment of Infectious, The Third Hospital of Jilin University, No. 126, Sendai Avenue, Changchun City, Jilin Province 130033, People’s Republic of ChinaTel +86-431-84995690Email [email protected]: The macrophage is one of the most important types of immune cells that protect against harmful stimuli. Macrophage activation plays a pivotal role in the progression and development of various inflammatory diseases. The neurokinin 1 receptor (NK-1R) is a G protein-coupled receptor that plays an important role in inflammatory diseases. Aprepitant is a kind of NK-1R antagonist. The purpose of this study is to determine the protective effect of aprepitant in lipopolysaccharide (LPS)-induced inflammatory responses in macrophages.Methods: We examined the anti-inflammatory and anti-oxidant effects of aprepitant in LPS-treated RAW264.7 macrophages by using real-time PCR, ELISA, and Western blot analysis. We also assessed cellular oxidative stress signaling by measuring the levels of cellular MDA, total ROS, and NADPH oxidase expression. Cellular NO production was measured by DAF-FM DA staining. The inhibitory effect of aprepitant against NF-κB signaling was evaluated by luciferase assay and Western blot analysis.Results: The expression of NK-1R is increased in LPS-induced macrophages, suggesting a potential role of the receptor in the inflammatory response. We show that aprepitant protects macrophages against oxidative stress by reducing the generation of ROS and the expression of NOX-4. Furthermore, aprepitant inhibits the secretion of pro-inflammatory cytokines and chemotactic factors by mediating the NF-κB signaling pathway.Conclusion: The NK-1R receptor antagonist aprepitant acts as an anti-inflammatory agent, indicating that the blockage of the NK-1R pathway in macrophages has the potential to suppress inflammation.Keywords: aprepitant, NK-1R, inflammation, NF-κB, oxidative stress
