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

Peptides derived from soricidin (C-peptides, eg SOR-C13 and SOR-C27), the paralytic peptide in saliva of theNorthern Short-tailed shrew (Blarina brevicauda) bind the calcium ion channel TRPV6 (Transient ReceptorPotential Vanilloid family number 6). Binding of the C-peptides to TRPV6 inhibits entry of calcium ions intothe cell that, in turn, modulates internal cell signalling pathways.The activity of the TRPV6 channel was significantly up-regulated in epithelial cells associated with cysticfibrosis 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 cysticfibrosis-associated epithelial cells by C-peptides modulates the secretion of cytokines (IL-6, IL-8 andRANTES) of the inflammatory pathway.The project's primary objective is to determine whether inhibiting TRPV6-mediated calcium entrance intoprimary 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 thecell. After optimization of the analytical protocols (ELISA testing), we will compare production of cytokinesand chemokines by epithelial cell lines derived from healthy lung (non-CF hAEC) and by lung cell linesderived from cystic fibrosis patients (CF hAEC) in the absence and presence of different doses of SOR-C27and SOR-C13, two peptide inhibitors of the TRPV6 calcium ion channel.