Calcitonin Gene-Related Peptide Induces IL-8 Synthesis in Human Corneal Epithelial Cells

• Published in: The Journal of immunology (1950) 2000-04, Vol.164 (8), p.4307-4312
• Main Authors: Tran, Mau T, Ritchie, Mary H, Lausch, Robert N, Oakes, John E
• Format: Article
• Language: English
• Subjects: Calcitonin Gene-Related Peptide - metabolism; Calcitonin Gene-Related Peptide - physiology; Cells, Cultured; Chemokine CCL2 - biosynthesis; Chemokine CCL2 - genetics; Chemokine CCL5 - biosynthesis; Chemokine CCL5 - genetics; Cyclic AMP - biosynthesis; Epithelium, Corneal - cytology; Epithelium, Corneal - immunology; Epithelium, Corneal - metabolism; Gene Expression Regulation - immunology; Humans; Interleukin-8 - biosynthesis; Interleukin-8 - genetics; monocyte chemotactic protein 1; Neurons, Afferent - immunology; Neurons, Afferent - metabolism; RANTES; Receptors, Calcitonin Gene-Related Peptide - biosynthesis; RNA - biosynthesis
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.164.8.4307

Calcitonin gene-related peptide (CGRP), a neuropeptide with proinflammatory activities, is released from termini of corneal sensory neurons in response to pain stimuli. Because neutrophil infiltration of the clear corneal surface is a hallmark of corneal inflammation in the human eye, we determined whether CGRP can bind to human corneal epithelial cells (HCEC) and induce expression of the neutrophil chemotactic protein IL-8. It was found that HCEC specifically bound CGRP in a saturable manner with a Kd of 2.0 x 10-9 M. Exposure of HCEC to CGRP induced a significant increase in intracellular cAMP levels and enhanced IL-8 synthesis nearly 4-fold. The capacity of CGRP to stimulate cAMP and IL-8 synthesis was abrogated in the presence of the CGRP receptor antagonist CGRP8-37. CGRP stimulation had no effect on the half-life of IL-8 mRNA while increasing IL-8 pre-mRNA synthesis >2-fold. In contrast to IL-8, CGRP did not induce monocyte chemotactic protein-1 or RANTES synthesis, nor did the neuropeptide enhance detectable increases in steady state levels of mRNA specific for these two beta-chemokines. The results suggest that HCEC possess CGRP receptors capable of initiating a signal transduction cascade that differentially activates expression of the IL-8 gene but not the genes for monocyte chemotactic protein-1 or RANTES. The capacity of CGRP to stimulate IL-8 synthesis in HCEC suggests that sensory neurons are involved in induction of acute inflammation at the eye surface.