Atherosclerosis is a pathogenic consequence of uncontrolled inflammation of the resident cells of vessel wall. Using cell-based model we showed that ribosomal protein L13a-dependent translational silencing pathway could terminate the expression of a group of inflammatory genes. In this proposal we will test whether this mechanism can resolve inflammation. We have demonstrated that IFN-3 induced synthesis of Ceruloplasmin (Cp) and a group of other inflammatory proteins in monocytic cells is under translational control. Further, we discovered a crucial role of ribosomal protein L13a and its release from 60S ribosome in the formation of IFN- Gamma-Activated Inhibitor of Translation (GAIT) complex. The translational silencing mechanism relies on the recognition of L13a-dependent GAIT complex by the GAIT element present in the 3 Uncontrolled inflammation is the cause of many diseases such as atherosclerosis or cardiovascular disease. This research will uncover the insight about the endogenous cellular mechanisms to control the expression of inflammatory molecules and help to generate novel therapeutic agents against inflammatory diseases.
Public Health Relevance
Uncontrolled inflammation is the cause of many diseases such as atherosclerosis or cardiovascular disease. This research will uncover the insight about the endogenous cellular mechanisms to control the expression of inflammatory molecules and help to generate novel therapeutic agents against inflammatory diseases.
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