PATHOGENIC MECHANISMS IN HUMAN URINARY TRACT CELLS

人类尿路细胞的致病机制

• 批准号: 3239850
• 负责人: John Wille
• 金额: $ 3.12万
• 依托单位: SOUTHERN RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-30 至 1989-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3239850
• 关键词: Escherichia coli; Proteus; Staphylococcus aureus; acrolein; cell adhesion; electron microscopy; epidermal growth factor; glycoproteins; human tissue; laboratory rat; lipopolysaccharides; ornithine decarboxylase; pathologic process; protein kinase C; proteoglycan; receptor binding; steroid hormone; tissue /cell culture; urinary tract infection

The etiology of the chronic urinary tract (UT) disease, interstitial cystitis, is obscure. The objective of the proposed research is to develop a suitable UT epithelial cell model by culturing normal human bladder and/or ureter uroepithelial (UE) cells in a serum- free medium. We also propose to employ this novel cell model to investigate the effect of bacterial-UE cell interactions on several different parameters affecting the capacity of the epithelial cells to transduce ligand-receptor binding signals. We plan to study the activation/inhibition of protein kinase-C (PK-C), and the induction/suppression of ornithine decarboxylase (ODC) before and after perturbation of the UE cells. Additional experimental protocols are designed to evaluate the effect of extrinsic cell signal modulators (e.g., bacterial adherence, bacterial and urinary metabolites, bacterial lipopolysaccharides) on the biosynthesis of proteoglycans. Experimental protocols are designed to investigate the effect of epidermal growth factor and steroid hormones (aldosterone, 17-beta-estradiol, testesterone, and progesterone) on signal-transducing enzymes, ODC and PK-C, and on the receptivity of UE cell binding to pathogenic bacteria (Escherichia coli, Proteus mirabilis, and Staphylococcus aureus). Lastly, we propose to investigate the effect of bacterial adherence, growth factors, hormones and the cyclophosphamide urinary metabolite, acrolein, on ion transport of UE cells in culture. In particular, experimental protocols are designed to study the regulation of both cation (Na+, K+), and anion (Cl-, and SO42-) uptake/efflux through the apical and basolateral surfaces of UE cells. We believe that these varied experimental protocols should provide new insights into the pathogenic mechanisms contributing to dysfunction of normal human UE cells of the bladder and UT.

慢性尿路（UT）疾病的病因，间质性