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Substance P Differentially Stimulates IL-8 Synthesis in Human Corneal Epithelial Cells

¹ From the Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland; and the ² Department of Microbiology and Immunology, College of Medicine, University of South Alabama, Mobile.

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) protein.

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 chemokine’s transcripts.

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