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The snake venom metalloproteinase BaP1 induces joint hypernociception through TNF-α and PGE2-dependent mechanisms
dc.creator | Fernandes, Cristina Maria | |
dc.creator | Teixeira, Catarina de Fátima | |
dc.creator | Leite, A. C. R. M. | |
dc.creator | Gutiérrez, José María | |
dc.creator | Rocha, F.A.C. | |
dc.date.accessioned | 2016-12-01T15:33:12Z | |
dc.date.available | 2016-12-01T15:33:12Z | |
dc.date.issued | 2007-08 | |
dc.identifier.citation | http://onlinelibrary.wiley.com/doi/10.1038/sj.bjp.0707351/abstract | |
dc.identifier.issn | 1476-5381 | |
dc.identifier.uri | https://hdl.handle.net/10669/29340 | |
dc.description.abstract | BACKGROUND AND PURPOSE: Matrix metalloproteinases (MMPs) have been implicated in joint tissue destruction in arthritis. However, MMPs have not been assigned a role in joint pain. We investigated the ability of BaP1, a metalloproteinase from Bothrops asper snake venom, with structural homology to MMPs, to induce joint hypernociception. EXPERIMENTAL APPROACH: Animals received intra-articular (i.art.) BaP1. Hypernociception was assessed using the rat-knee joint articular incapacitation test. Cell influx, prostaglandin E(2) (PGE(2)), and TNF-alpha levels were assessed in joint exudates following BaP1 injection. KEY RESULTS: BaP1 (5 microg per joint) provoked hypernociception between 1 and 6 h after i.art. injection. Cell influx, mostly neutrophils, was maximal 3 h after BaP1 i.art. injection. BaP1 also led to increase in PGE(2) and TNF-alpha levels in the joint exudates. Pretreatment with either indomethacin (4 mg.kg(-1) i.p.) or with an anti-TNF-alpha antiserum (i.art.) significantly inhibited both BaP1-induced joint hypernociception and cell influx. In isolated rat peritoneal macrophages, BaP1 increased cyclooxygenase (COX)-2 expression, while not altering that of COX-1. CONCLUSIONS AND IMPLICATIONS: This is the first demonstration that a metalloproteinase promotes joint hypernociception. This effect involves local release of PGE(2) and TNF-alpha. BaP1-induced increase in PGE(2) is associated to increased COX-2 expression in macrophages. Blocking PGE(2) or TNF-alpha inhibits BaP1-induced hypernociception. In addition to unravelling a hitherto unknown mechanism whereby TNF blockade provides analgesia in arthritis, the data show, for the first time that MMPs are involved in inflammatory joint hypernociception and induce COX-2 expression. | es_ES |
dc.description.sponsorship | Fundação de Amparo à Pesquisa do Estado de São Paulo//FAPESP/Brasil | es_ES |
dc.description.sponsorship | Universidad de Costa Rica//UCR/Costa Rica | es_ES |
dc.language.iso | en_US | es_ES |
dc.source | British Journal of Pharmacology; Volumen 151, Número 8. 2007 | es_ES |
dc.subject | Metalloproteinase BaP1 | es_ES |
dc.subject | Hyperalgesia | es_ES |
dc.subject | Synovial Joint | es_ES |
dc.subject | Arthritis | es_ES |
dc.subject | TNF-α | es_ES |
dc.subject | Prostaglandins | es_ES |
dc.title | The snake venom metalloproteinase BaP1 induces joint hypernociception through TNF-α and PGE2-dependent mechanisms | es_ES |
dc.type | artículo original | |
dc.identifier.doi | 10.1038/sj.bjp.0707351 | |
dc.description.procedence | UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP) | es_ES |
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