A role of TRPV6 calcium channel inhibition on cytokine and chemokine production by epithelial cells

TRPV6钙通道抑制对上皮细胞细胞因子和趋化因子产生的作用

• 批准号: 485506-2015
• 负责人: Lin, TongJun
• 金额: $ 1.82万
• 依托单位: Dalhousie University
• 依托单位国家: 加拿大
• 项目类别: Engage Grants Program
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=585007
• 关键词: role; TRPV6; calcium; channel; inhibition

Peptides derived from soricidin (C-peptides, eg SOR-C13 and SOR-C27), the paralytic peptide in saliva of the Northern Short-tailed shrew (Blarina brevicauda) bind the calcium ion channel TRPV6 (Transient Receptor Potential Vanilloid family number 6). Binding of the C-peptides to TRPV6 inhibits entry of calcium ions into the cell that, in turn, modulates internal cell signalling pathways. The activity of the TRPV6 channel was significantly up-regulated in epithelial cells associated with cystic fibrosis inflammatory response. However, whether C-peptides regulate epithelial cell function is not known. The study proposed here is to investigate for the first time that whether inhibition of TRPV6 in cystic fibrosis-associated epithelial cells by C-peptides modulates the secretion of cytokines (IL-6, IL-8 and RANTES) of the inflammatory pathway. The project's primary objective is to determine whether inhibiting TRPV6-mediated calcium entrance into primary cystic fibrosis cells reduces the production of inflammatory cytokines (IL-6 and IL-8) and chemokines (RANTES). TRPV6 functions as a calcium ion channel at the cell membrane, controlling calcium flow into the cell. After optimization of the analytical protocols (ELISA testing), we will compare production of cytokines and chemokines by epithelial cell lines derived from healthy lung (non-CF hAEC) and by lung cell lines derived from cystic fibrosis patients (CF hAEC) in the absence and presence of different doses of SOR-C27 and SOR-C13, two peptide inhibitors of the TRPV6 calcium ion channel.

来自soricidin的肽（C肽，例如SOR-C13和SOR-C27），其是在哺乳动物唾液中的麻痹肽。 北方短尾鼩（Blarina brevicauda）结合钙离子通道TRPV 6（瞬时受体 可能的Vanilloid家族编号6）。C肽与TRPV 6的结合抑制钙离子进入TRPV 6。 这种细胞反过来又调节内部细胞信号通路。 TRPV 6通道的活性在与囊性癌相关的上皮细胞中显著上调， 纤维化炎症反应。然而，C肽是否调节上皮细胞功能尚不清楚。 本研究旨在首次研究抑制TRPV 6在囊性癌中的表达是否与肿瘤的发生有关。 通过C-肽调节纤维化相关上皮细胞的细胞因子（IL-6、IL-8和IL-10）的分泌， RANTES）的炎症途径。 该项目的主要目的是确定是否抑制TRPV 6介导的钙进入 原发性囊性纤维化细胞减少炎性细胞因子（IL-6和IL-8）和趋化因子的产生 （RANTES）。TRPV 6作为细胞膜上的钙离子通道发挥作用，控制钙流入细胞膜。 cell.在优化分析方案（ELISA检测）后，我们将比较细胞因子的产生 来源于健康肺的上皮细胞系（非CF hAEC）和肺细胞系（非CF hAEC） 在不存在和存在不同剂量的SOR-C27的情况下， 和SOR-C13，TRPV 6钙离子通道的两种肽抑制剂。