Inflammatory bowel disease (IBD) is a debilitating inflammatory condition of the colon and small bowel of unknown etiology. Inflammation is associated with alterations in the permeability of the microvascular endothelium and is accompanied by endothelial cell proliferation, but the mechanisms responsible for these changes are unknown. The role of the microvascular endothelial cell in normal and pathologic inflammation has been studied in many tissues other than the colon, including the retina, skin, brain and lungs. These studies have been performed in animal models and in isolated cell culture. However, the role of the endothelial cell in inflammation of the colon has been more difficult to elucidate because there have not been good animal models for colonic inflammation and isolated endothelial cells have not survived contamination from the non-sterile colonic environment and overgrowth of competing cell types. Further, endothelial cell lines, readily available and inexpensive, cannot be used as a substitute due to differences in the endothelium between tissues. We hypothesize that inflammatory bowel disease (IBD) is associated with abnormalities in the permeability characteristics and growth responses of intestinal endothelial cells. Thus, investigation of permeability and growth responses of endothelial cells from normal colon will provide the basic information necessary to define the alterations in regulation and control of endothelial cells in the inflamed state and provide insight into abnormal regulation of endothelial cells in uncontrolled inflammation. Normal human colonic microvascular endothelial cells (HuCMECs) have been isolated in our lab. We now propose to characterize these cells by determining the optimal conditions for growth, baseline chemotaxis, capillary tube formation, gene expression and endothelial permeability. In addition, we will determine the effects of inflammatory mediators, such as substance P and bradykinin, and growth factors such as vEOF and bFUF, on these baseline cell properties. These studies will lead to a clearer understanding of the regulation of normal colonic endothelial cells and will provide baseline information necessary tc proceed with studies of endothelial cells from patients with inflammatory bowel disease. Furthermore interventions that target the cell, or the factors that act directly on the cell, may lead to novel therapeutic interventions in these poorly understood diseases.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Clinical Investigator Award (CIA) (K08)
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Special Emphasis Panel (SRC)
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Podskalny, Judith M,
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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