title: Cyclooxygenase-2 and Prostaglandin E2 Signaling through Prostaglandin Receptor EP-2 Favor the Development of Myocarditis during Acute Trypanosoma cruzi Infection.
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 CD11b+Ly6G- cells purified from infected heart tissue express COX-2 and produce prostaglandin E2 (PGE2) ex vivo. T. cruzi infections in COX-2 or PGE2-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.
authors: Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Madrid, Spain.
authors: Néstor A
authors: NA
authors: Guerrero
authors: Institut de Recerca de l'Hospital de la Santa Creu i de Sant Pau, Barcelona, Spain.
authors: Mercedes
authors: M
authors: Camacho
authors: Institut de Recerca de l'Hospital de la Santa Creu i de Sant Pau, Barcelona, Spain.
authors: Luis
authors: L
authors: Vila
authors: Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Madrid, Spain; Instituto de Investigación Sanitaria de la Princesa, Madrid, Spain.
authors: Miguel A
authors: MA
authors: Íñiguez
authors: Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Madrid, Spain.
authors: Carlos
authors: C
authors: Chillón-Marinas
authors: Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Madrid, Spain; Department of Obstetrics/Gynecology, Columbia University Medical Center, Columbia University, New York, New York, United States of America.
authors: Henar
authors: H
authors: Cuervo
authors: Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Madrid, Spain.
authors: Cristina
authors: C
authors: Poveda
authors: Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Madrid, Spain; Instituto de Investigación Sanitaria de la Princesa, Madrid, Spain.
authors: Manuel
authors: M
authors: Fresno
authors: Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Madrid, Spain; Instituto de Investigación Sanitaria de la Princesa, Madrid, Spain.
authors: Núria
authors: N
authors: Gironès
mesh_terms: D000818:Animals; D014355:Chagas Disease / Q000150:complications / Q000201:enzymology / Q000235:genetics / Q000276:immunology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D015232:Dinoprostone / Q000276:immunology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009205:Myocarditis / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D009206:Myocardium / Q000201:enzymology / Q000276:immunology; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000235:genetics / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000276:immunology / Q000502:physiology*
chemical_list: D016207:Cytokines; C545645:Ptger2 protein, mouse; D058307:Receptors, Prostaglandin E, EP2 Subtype; D051546:Cyclooxygenase 2; D015232:Dinoprostone