Calcitonin gene-related peptide induces IL-8 synthesis in human corneal epithelial cells.

Abstract

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.

• Authors: M T Tran, M H Ritchie, R N Lausch, J E Oakes
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 164 Issue 8 Pg. 4307-12 (Apr 15 2000) ISSN: 0022-1767 [Print] United States
• PMID: 10754330 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Chemokine CCL2
• Chemokine CCL5
• Interleukin-8
• Receptors, Calcitonin Gene-Related Peptide
• RNA
• Cyclic AMP
• Calcitonin Gene-Related Peptide

Topics

• Calcitonin Gene-Related Peptide (metabolism, physiology)
• Cells, Cultured
• Chemokine CCL2 (biosynthesis, genetics)
• Chemokine CCL5 (biosynthesis, genetics)
• Cyclic AMP (biosynthesis)
• Epithelium, Corneal (cytology, immunology, metabolism)
• Gene Expression Regulation (immunology)
• Humans
• Interleukin-8 (biosynthesis, genetics)
• Neurons, Afferent (immunology, metabolism)
• RNA (biosynthesis)
• Receptors, Calcitonin Gene-Related Peptide (biosynthesis)