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

M  Steinhoff; N  Vergnolle; S H  Young; M  Tognetto; S  Amadesi; H S  Ennes; M  Trevisani; M D  Hollenberg; J L  Wallace; G H  Caughey; Sharon Elizabeth Mitchell; Lynda Williams; P  Geppetti; E A  Mayer; N W  Bunnett

doi:10.1038/72247

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

M Steinhoff, N Vergnolle, S H Young, M Tognetto, S Amadesi, H S Ennes, M Trevisani, M D Hollenberg, J L Wallace, G H Caughey, Sharon Elizabeth Mitchell, Lynda Williams, P Geppetti, E A Mayer, N W Bunnett

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English
Pages (from-to)	151-158
Number of pages	8
Journal	Nature Medicine
Volume	6
Issue number	2
DOIs	https://doi.org/10.1038/72247
Publication status	Published - Feb 2000

Keywords

gene-related peptide
mast-cell tryptase
spinal dorsal horn
substance-P
endothelial-cells
thrombin receptor
in-vitro
skin
vasodilator
CGRP

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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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., Geppetti, P., Mayer, E. A., & Bunnett, N. W. (2000). Agonists of proteinase-activated receptor 2 induce inflammation by a neurogenic mechanism. Nature Medicine, 6(2), 151-158. https://doi.org/10.1038/72247

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title = "Agonists of proteinase-activated receptor 2 induce inflammation by a neurogenic mechanism",

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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T1 - Agonists of proteinase-activated receptor 2 induce inflammation by a neurogenic mechanism

AU - Steinhoff, M

AU - Vergnolle, N

AU - Young, S H

AU - Tognetto, M

AU - Amadesi, S

AU - Ennes, H S

AU - Trevisani, M

AU - Hollenberg, M D

AU - Wallace, J L

AU - Caughey, G H

AU - Mitchell, Sharon Elizabeth

AU - Williams, Lynda

AU - Geppetti, P

AU - Mayer, E A

AU - Bunnett, N W

PY - 2000/2

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N2 - 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.

AB - 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.

KW - gene-related peptide

KW - mast-cell tryptase

KW - spinal dorsal horn

KW - substance-P

KW - endothelial-cells

KW - thrombin receptor

KW - in-vitro

KW - skin

KW - vasodilator

KW - CGRP

U2 - 10.1038/72247

DO - 10.1038/72247

M3 - Article

SN - 1546-170X

VL - 6

SP - 151

EP - 158

JO - Nature Medicine

JF - Nature Medicine

IS - 2

ER -

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

Abstract

Keywords

UN SDGs

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