Preventing HBV-Associated Liver Injury with Specialized Proresolving Mediators
Abstract
This research is relevant to the Topic Area “Hepatitis B and C.” Hepatitis B virus (HBV) infection affects more than 240 million people worldwide, including an estimated 1-2 million people in the United States. Infection with HBV increases the risk for developing serious diseases such as liver scarring (cirrhosis) and cancer. Because HBV is transmitted through infected blood, military personnel are at risk for contracting HBV, particularly in countries where the prevalence of the virus is high. In addition, military Veterans are disproportionately affected by HBV infection. The overall prevalence rate of HBV infection in Veterans is estimated to be approximately two times greater than that of the general population, and some populations of Veterans have current or prior infection rates that are even higher. Current therapies for hepatitis B reduce but rarely eliminate the virus, even after long-term therapy with antiviral drugs. Therefore, new treatment options for HBV infection are urgently needed. Small molecules known as specialized pro-resolving lipid mediators (SPMs) play important roles in halting damaging inflammatory reactions that occur when the immune system reacts to viruses and bacteria. SPMs regulate the activity of immune cells by binding to receptors on the cells and promoting activities that help in healing inflamed tissues. In this study, we will employ a mouse model of HBV-associated liver inflammation to examine the hypothesis that SPMs can promote the resolution of inflammation and prevent the liver damage that is associated with HBV infection. We will then perform experiments to understand the underlying cellular and molecular basis for the effects of SPMs on inflammation in the liver. The proposed research is innovative because it focuses on understanding unknown relationships between SPMs and the resolution of inflammation that occurs in the HBV-infected liver, which may establish SPMs as potential therapeutic molecules for preventing HBV-associated liver injury. The proposed research is significant because an effective therapy that prevents HBV-associated liver damage could have a substantial impact on the prevention of liver diseases. The impact of this proposal also lies in the fact that these studies will lead to new understanding of the role of SPMs in liver damage, which could have implications for designing therapeutic approaches for other viral infections and inflammatory diseases as well.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810186
Entities
People
- Michael Robek
Organizations
- Albany Medical College
- United States Army