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

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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.