Abstract 7477: Isoxanthohumol inhibits LPS-induced inflammatory responses in macrophages

Abstract

Abstract Background: Pathogen infection, such as bacteria, viruses, and fungus, frequently leads to septicemia through a series of inflammatory responses that have very high fatality rates. And, servere inflammation may cause gene mutation which is beginning of cancer. Macrophages are a critical type of antigen-presenting cells that control both innate and adaptive immune responses. During pathogen infection, activated macrophages secret many proinflammatory mediators and cytokines, including nitric oxide (NO), TNF-α and IL-6 against pathogens; however, an overwhelming inflammatory response provokes abundant cells to undergo apoptosis. In the present study, we aimed to examine the anti-inflammatory effect of isoxanthohumol, a prenylflavonoid from hops and beer. Method: We used lipopolysaccharide (LPS) as a pathogenic stimulus to induce inflammatory responses by J774A.1 macrophages. MTT assay was used to detect cell viability. The secretion of NO was analyzed by Griess reagent assay, while the production of TNF-α, IL-6, IL-1β was measured by enzyme-linked immunosorbent assay (ELISA). The expression of iNOS, COX-2, and MAPKs was examined by Western blotting. The activity of NF-κB was analyzed by promotor reporter assay. The activation of NLRP3 inflammasome was examined by ELISA and immunofluorescence staining. In addition to that, we explored the secretion of cytokines, IL-1β, in THP-1 cell. Result: We found that isoxanthohumol significantly suppresses the secretion of NO and attenuates the production of TNF-α and IL-6 by LPS-induced macrophages. In addition, isoxanthohumol also inhibits the expression of iNOS and COX-2, suppresses the phosphorylation of JNK, and attenuates the activity of NF-κB by LPS-induced macrophages. Moreover, isoxanthohumol decreases the activation of NLRP3 inflammasome by reducing the production of IL-1β and repressing the ASC speck formation of NLRP3 inflammasome in LPS/ATP-induced macrophages. Conclusion: Our experimental results demonstrated that isoxanthohumol effectively inhibits LPS-induced inflammatory responses in macrophages, suggesting that isoxanthohumol might have benefits for attenuating inflammation. Citation Format: Tzu-Han Kao, Chia-yang Li. Isoxanthohumol inhibits LPS-induced inflammatory responses in macrophages [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7477.