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Nat Med. 2000 Feb;6(2):151-8.

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

Author information

1
Department of Surgery and Physiology, University of California, San Francisco, CA 94143, USA.

Abstract

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.

PMID:
10655102
DOI:
10.1038/72247
[Indexed for MEDLINE]

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