Cyclooxygenase-2 and prostaglandin E2 signaling through prostaglandin receptor EP- 2 favor the development of myocarditis during acute trypanosoma cruzi infection
Guerrero, Néstor A. (Centro de Biología Molecular Severo Ochoa (Madrid, Espanya))
Camacho, Mercedes (Institut d'Investigació Biomèdica Sant Pau)
Vila, Luis (Institut d'Investigació Biomèdica Sant Pau)
Íñiguez, Miguel A. (Instituto de Investigación Sanitaria de la Princesa (Madrid, Espanya))
Chillón-Marinas, Carlos (Centro de Biología Molecular Severo Ochoa (Madrid, Espanya))
Cuervo, Henar (Columbia University)
Poveda, Cristina (Centro de Biología Molecular Severo Ochoa (Madrid, Espanya))
Fresno, Manuel (Instituto de Investigación Sanitaria de la Princesa (Madrid, Espanya))
Gironès, Núria (Instituto de Investigación Sanitaria de la Princesa (Madrid, Espanya))
Universitat Autònoma de Barcelona

Date:	2015
Abstract:	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.
Grants:	Ministerio de Ciencia e Innovación PS09/00538
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	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
Published in:	PLoS neglected tropical diseases, Vol. 9 Núm. 8 (2015) , p. A016, ISSN 1935-2735

DOI: 10.1371/journal.pntd.0004025
PMID: 26305786

23 p, 15.1 MB

The record appears in these collections:
Articles > Research articles
Articles > Published articles