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Mau T. Tran, Robert N. Lausch, John E. Oakes; Substance P Differentially Stimulates IL-8 Synthesis in Human Corneal Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2000;41(12):3871-3877.
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purpose. To determine whether substance P (SP), a neuropeptide with
proinflammatory properties, specifically interacts with human corneal
epithelial cells to stimulate synthesis of the chemokines interleukin
(IL)-8, monocyte chemo-attractant protein (MCP)-1, and
regulated on activation normal T-cell expressed and secreted (RANTES)
methods. Primary cultures of human corneal epithelial cells were established
from human corneas. Expression of the SP receptor neurokinin (NK)-1 was
determined by both the reverse transcription–polymerase chain reaction
(RT-PCR) and radiolabeled saturation binding experiments. Synthesis of
chemokine-specific RNA in cells stimulated with SP was analyzed by
RT-PCR, and quantitation of chemokine protein synthesis was achieved by
enzyme-linked immunosorbent assay.
results. Human corneal epithelial cells expressed NK-1 mRNA and bound SP with a K d characteristic of NK-1. Exposure of cells
to SP had no effect on IL-8–specific mRNA synthesis, whereas it
increased the half-life of IL-8 transcripts by more than twofold,
resulting in significant enhancement of IL-8 synthesis. The capacity of
SP to bind to corneal epithelial cells and to induce IL-8 synthesis was
abrogated in the presence of a specific NK-1 receptor antagonist. In
contrast to IL-8, exposure of cells to SP did not stimulate synthesis
of MCP-1 or RANTES.
conclusions. The results suggest that human corneal cells express NK-1 receptors
that specifically bind SP and induce IL-8 synthesis by stabilizing the
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