Using activators of NF-KB to model inflammation

Chronic inflammation underlies many chronic diseases such as obesity and diabetes and can lead to vascular and organ dysfunction, disability and death. Inflammation has been widely studied due to its broad involvement in numerous disease states, but current models of inflammation suffer from limitations. Models such as LPS treatment are non-specific and require multiple doses over extended periods of time which can lead to septic shock. The goal of our study was to develop an alternative model offering cell and organ specificity using an AAV-based approach. We hypothesize that delivering Ikk2, a potent activator of NF-KB will lead to chronic inflammation in the targeted cells and tissues. This approach has the benefit of cell and tissue specificity using specialized promoters and modified AAV capsids. Additionally, it will allow for consistent and regulatable expression over time. In preliminary studies I compared two know activators of NFKB, IKBKE and IKK2 to investigate differences in expression of inflammatory markers. Western blot analysis revealed ICAM-1 and IRF-1 protein levels were increased with IKK2 expression. In comparison, the inhibitior of apoptosis, CIAP-2, was more highly increased under IKBKE expression. We conclude that IKK2 would be more suitable to induce inflammation in target cells. Future studies will employ qPCR, Western blot, cytokine analysis and vascular function studies to characterize the effects in vivo. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.