12-HETE is a regulator of PGE2 production via COX-2 expression induced by a snake venom group IIA phospholipase A2 in isolated peritoneal macrophages
dc.creator | Moreira, Vanessa | |
dc.creator | Gutiérrez, José María | |
dc.creator | Lomonte, Bruno | |
dc.creator | Ramirez Vinolo, Marco Aurélio | |
dc.creator | Curi, Rui | |
dc.creator | Lambeau, Gérard | |
dc.creator | Teixeira, Catarina de Fátima | |
dc.date.accessioned | 2021-03-02T20:13:14Z | |
dc.date.available | 2021-03-02T20:13:14Z | |
dc.date.issued | 2020 | |
dc.description.abstract | The snake venom myotoxin (MT)-III is a group IIA secreted phospholipase A2 (sPLA2) with pro-inflammatory activities. Previous studies have demonstrated that MT-III has the ability to stimulate macrophages to release inflammatory lipid mediators derived from arachidonic acid metabolism. Among them, we highlight prostaglandin (PG)E2 produced by the cyclooxygenase (COX)-2 pathway, through activation of nuclear factor (NF)-κB. However, the mechanisms coordinating this process are not fully understood. This study investigates the regulatory mechanisms exerted by other groups of bioactive eicosanoids derived from 12-lipoxygenase (12-LO), in particular 12-hydroxyeicosatetraenoic (12-HETE), on group IIA sPLA2-induced (i) PGE2 release, (ii) COX-2 expression, and (iii) activation of signaling pathways p38 mitogen-activated protein kinases(p38MAPK), protein C kinase (PKC), extracellular signal-regulated kinase 1/2 (ERK1/2), and NF-κB. Stimulation of macrophages with group IIA sPLA2 resulted in release of 12-HETE without modification of 12-LO protein levels. Pre-treatment of these cells with baicalein, a 12-LO inhibitor, decreased the sPLA2-induced PGE2 production, significantly reduced COX-2 expression, and inhibited sPLA2-induced ERK; however, it did not affect p38MAPK or PKC phosphorylation. In turn, sPLA2-induced PGE2 release and COX-2 expression, but not NF-κB activation, was attenuated by pre-treating macrophages with PD98059 an inhibitor of ERK1/2. These results suggest that, in macrophages, group IIA sPLA2-induced PGE2 release and COX-2 protein expression are distinctly mediated through 12-HETE followed by ERK1/2 pathway activation, independently of NF-κB activation. These findings highlight an as yet undescribed mechanism by which 12-HETE regulates one of the distinct signaling pathways for snake venom group IIA sPLA2-induced PGE2 release and COX-2 expression in macrophages. | es_ES |
dc.description.procedence | UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP) | es_ES |
dc.description.sponsorship | Fundación de Apoyo a la Investigación del Estado de Sao Paulo/[07/03336-9]/FAPESP/Brasil | es_ES |
dc.description.sponsorship | Consejo Nacional de Desarrollo Científico y Tecnológico/[306099/2008-0]/CNPq/Brasil | es_ES |
dc.description.sponsorship | Fundación de Apoyo a la Investigación del Estado de Sao Paulo/[07/03337-5]/FAPESP/Brasil | es_ES |
dc.description.sponsorship | Consejo Nacional de Desarrollo Científico y Tecnológico/[202077/2008-0]/CNPq/Brasil | es_ES |
dc.description.sponsorship | Fundación de Apoyo a la Investigación del Estado de Sao Paulo/[12/10653-9]/FAPESP/Brasil | es_ES |
dc.identifier.citation | https://www.sciencedirect.com/science/article/abs/pii/S0009279719312086?via%3Dihub | |
dc.identifier.doi | 10.1016/j.cbi.2019.108903 | |
dc.identifier.issn | 0009-2797 | |
dc.identifier.uri | https://hdl.handle.net/10669/82938 | |
dc.language.iso | eng | es_ES |
dc.rights | acceso abierto | es_ES |
dc.source | Chemico-Biological Interactions, vol.317, pp.1-9 | es_ES |
dc.subject | Snake venom group IIA phospholipase A2 | es_ES |
dc.subject | Prostaglandin E2 | es_ES |
dc.subject | Cyclooxygenase-2 | es_ES |
dc.subject | 12-Hydroxyeicosatetraenoic acid | es_ES |
dc.subject | 12-Lipoxygenase | es_ES |
dc.subject | Macrophages | es_ES |
dc.title | 12-HETE is a regulator of PGE2 production via COX-2 expression induced by a snake venom group IIA phospholipase A2 in isolated peritoneal macrophages | es_ES |
dc.type | artículo original |
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