Agonists of proteinase-activated receptor 2 induce inflammation by a neurogenic mechanism |
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| Authors: | 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 Bunnett N W |
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| Affiliation: | Department of Surgery and Physiology, University of California, San Francisco, CA 94143, USA. |
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| 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. |
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