The post-transcriptional regulation of IL-1beta will be studied in this project. IL-1beta is a proinflammatory cytokine which exerts pleiotropic effects on various cell systems. These effects include the stimulation of immune cells in response to viral or bacterial infection. The inappropriate expression of IL-1beta, however, can lead to autoimmune diseases, including diabetes and inflammatory bowel disease. The molecular characterization of the posttranscriptional regulation of IL-1beta will lead to better understanding of IL-1beta gene regulation, the molecular basis for these diseases, and to the design of therapeutic strategies for the control of such diseases vis-a'-vis IL-1beta. A model cell system, the mouse macrophage cell line J774.1 will be used to study the post-transcriptional regulation of IL-1beta. When a mouse macrophage cell line such as J774.1 is infected with virus such as the mouse hepatitis virus (MHV), the translation of most host mRNAs decreases with the exception of IL-1beta mRNA, whose translation is augmented. This translational response does not occur in non-macrophage cell lines such as L cells. Our preliminary results indicate the participation of IL-1beta UTRs in conjunction with specific RNA binding proteins in translation phenomenon. The characterization of this unusual translational response in MHV infected macrophage cell lines, used as a model system, will help us to better understand the post- transcriptional regulation of IL-1beta gene regulation.
