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Agonists of proteinase-activated receptor 2 induce inflammation by a neurogenic mechanism

Steinhoff, M., Vergnolle, N., Young, S. H., Tognetto, M., Amadesi, S., Ennes, H. S., Trevisani, M., Hollenberg, M. D., Wallace, J. L., Caughey, G. H., Mitchell, S. E., Williams, L. M., Geppetti, P., Mayer, E. A. and Bunnett, N. W. (2000) Agonists of proteinase-activated receptor 2 induce inflammation by a neurogenic mechanism. Nature medicine, 6 (2). pp. 151-158. ISSN 1078-8956

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To link to this item DOI: 10.1038/72247

Abstract/Summary

Trypsin and mast cell tryptase cleave proteinase-activated receptor 2 and, by unknown mechanisms, induce widespread inflammation. We found that a large proportion of primary spinal afferent neurons, which express proteinase-activated receptor 2, also contain the proinflammatory neuropeptides calcitonin gene-related peptide and substance P. Trypsin and tryptase directly signal to neurons to stimulate release of these neuropeptides, which mediate inflammatory edema induced by agonists of proteinase-activated receptor 2. This new mechanism of protease-induced neurogenic inflammation may contribute to the proinflammatory effects of mast cells in human disease. Thus, tryptase inhibitors and antagonists of proteinase-activated receptor 2 may be useful anti-inflammatory agents.

Item Type:Article
Refereed:Yes
Divisions:No Reading authors. Back catalogue items
Faculty of Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Division of Pharmacology
ID Code:35823
Publisher:Nature publishing group

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