VCAM-1 is a cytokine inducible, endothelial leukocyte adhesion molecule. It specifically binds the integrin VLA4, which is restricted to monocytes, lymphocytes, eosinophils and basophils but is not present on neutrophils. Immunohistochemical techniques reveal endothelial VCAM-1 expression associated with a variety of inflammatory processes including vasculitic lesions, chronic vascular graft rejection, and early atherosclerosis. The laboratory has begun preliminary efforts to elucidate the molecular mechanisms controlling VCAM-1 response to cytokine and tissue specific expression. This proposal involves three lines of investigation and will expand upon previous experiments. First, analysis of novel functional elements in the promoter region of the VCAM1 gene to better understand the DNA-protein interactions that mediate the transcriptional regulation of VCAM1. Second, characterization of the DNA binding and transactivating properties of a novel transcription factor. The candidate factor was obtained by screening an expression library with a recognition site sequence contained within the VCAM1 promoter. Third, utilization of characterized promoter sequences as transgenes to allow a more stringent evaluation of the temporal and spatial (cell-type specific) expression pattern of VCAM1. Elucidation of the mechanisms governing VCAM-1 expression will further our understanding of the inflammatory response and possibly suggest points of intervention.
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