MODULATION OF AIRWAY EPITHELIAL CYTOKINE RECEPTOR FUNCTION

气道上皮细胞因子受体功能的调节

• 批准号: 5201080
• 负责人: S LEVINE
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5201080
• 关键词: cytokine receptors; dexamethasone; enzyme activity; enzyme induction /repression; enzyme mechanism; human tissue; inflammation; interleukin 1; phorbols; protease inhibitor; protein kinase C; receptor binding; receptor expression; respiratory epithelium; tissue /cell culture; tumor necrosis factor alpha

Airway epithelial cells express receptors for the proinflammatory cytokines TNF-alpha and IL-1beta. Cells may modulate cytokine responses by the alteration of cellular receptor numbers or affinity. Airway epithelial cells express the P55 TNFalpha receptor. Protein Kinase C activation by phorbol ester in a human epithelial cell line or in human airway epithelial cells in primary culture results in the solubilization of cell surface P55 TNFalpha receptors. Similarly IL-1beta treatment of airway epithelial cells induces the shedding of TNFalpha P55 receptors. This effect is inhibited by pretreatment of the cells with the PKC antagonist calphostin C. Conversely, dexamethasone treatment of epithelial cells results in an increase in cell associated TNFalpha receptor protein and in a reduction of TNFalpha receptor shedding. One manuscript has been prepared and studies are in progress to investigate the mechanisms of PKC induced TNFalpha receptor shedding as well as other mechanisms of epithelial cell modulation of cytokine responses. A knowledge of the mechanisms by which epithelial cells may modulate responses to inflammatory cytokines may allow for new therapeutic approaches to the reduction of airway inflammation.

气道上皮细胞表达促炎因子受体 细胞因子TNF-α和IL-1 β。细胞可以通过以下方式调节细胞因子应答： 细胞受体数量或亲和力的改变。气道上皮 细胞表达P55 TNF α受体。蛋白激酶C激活 人上皮细胞系或人气道中佛波酯 原代培养中的上皮细胞导致细胞溶解 表面P55 TNF α受体。类似地，气道IL-1 β治疗 上皮细胞诱导TNF α P55受体的脱落。这 用PKC拮抗剂预处理细胞可抑制这种作用 钙磷素C相反，地塞米松治疗上皮细胞 导致细胞相关TNF α受体蛋白的增加， TNF α受体脱落减少。其中一份手稿 研究正在进行中，以研究PKC的机制。 诱导的TNF α受体脱落以及其他 上皮细胞调节细胞因子应答。的知识 上皮细胞可能调节对 炎性细胞因子可能允许新的治疗方法， 减轻气道炎症。