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

被引：752

作者：

Steinhoff, M

Vergnolle, N

Young, SH

Tognetto, M

Amadesi, S

Ennes, HS

Trevisani, M

Hollenberg, MD

Wallace, JL

Caughey, GH

Mitchell, SE

Williams, LM

Geppetti, P

Mayer, EA

Bunnett, NW

机构：

[1] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA

[2] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA

[3] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA

[4] Univ Calif San Francisco, Inst Cardiovasc Res, San Francisco, CA 94143 USA

[5] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90073 USA

[6] Univ Calif Los Angeles, CURE VA UCLA Digest Dis Res Ctr, Los Angeles, CA 90073 USA

[7] Univ Calgary, Dept Pharmacol & Therapeut, Calgary, AB T2N 4N1, Canada

[8] Rowett Res Inst, Aberdeen LS21 9JT, Scotland

[9] Univ Ferrara, Dept Expt & Clin Med, Headache Ctr, Pharmacol Sect, I-44100 Ferrara, Italy

来源：

NATURE MEDICINE | 2000年 / 6卷 / 02期

基金：

美国国家卫生研究院; 英国医学研究理事会;

关键词：

D O I：

10.1038/72247

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：151 / 158

页数：8

共 45 条

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