Cyclooxygenase-2 and prostaglandin E2 signaling through prostaglandin receptor EP- 2 favor the development of myocarditis during acute trypanosoma cruzi infection
Inflammation plays an important role in the pathophysiology of Chagas disease, caused by Trypanosoma cruzi. Prostanoids are regulators of homeostasis and inflammation and are produced mainly by myeloid cells, being cyclooxygenases, COX-1 and COX-2, the key enzymes in their biosynthesis from arachido...
| Autores: | , , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2015 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:299426 |
| Acceso en línea: | https://ddd.uab.cat/record/299426 https://dx.doi.org/urn:doi:10.1371/journal.pntd.0004025 |
| Access Level: | acceso abierto |
| Palabra clave: | Animals Chagas Disease Cyclooxygenase 2 Cytokines Dinoprostone Humans Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Myocarditis Myocardium Receptors, Prostaglandin E, EP2 Subtype Trypanosoma cruzi |
| Sumario: | Inflammation plays an important role in the pathophysiology of Chagas disease, caused by Trypanosoma cruzi. Prostanoids are regulators of homeostasis and inflammation and are produced mainly by myeloid cells, being cyclooxygenases, COX-1 and COX-2, the key enzymes in their biosynthesis from arachidonic acid (AA). Here, we have investigated the expression of enzymes involved in AA metabolism during T. cruzi infection. Our results show an increase in the expression of several of these enzymes in acute T. cruzi infected heart. Interestingly, COX-2 was expressed by CD68 myeloid heart-infiltrating cells. In addition, infiltrating myeloid CD11bLy6G cells purified from infected heart tissue express COX-2 and produce prostaglandin E (PGE) ex vivo. T. cruzi infections in COX-2 or PGE- dependent prostaglandin receptor EP-2 deficient mice indicate that both, COX-2 and EP-2 signaling contribute significantly to the heart leukocyte infiltration and to the release of chemokines and inflammatory cytokines in the heart of T. cruzi infected mice. In conclusion, COX-2 plays a detrimental role in acute Chagas disease myocarditis and points to COX-2 as a potential target for immune intervention. |
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