Cyclooxygenase-2 and Prostaglandin E-2 Signaling through Prostaglandin Receptor EP-2 Favor the Development of Myocarditis during Acute Trypanosoma cruzi Infection
Por:
Guerrero, NA, Camacho, M, Vila, L, Iniguez, MA, Chillon-Marinas, C, Cuervo, H, Poveda, C, Fresno, M, Girones, N
Publicada:
1 ago 2015
Resumen:
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 E-2 (PGE(2)) ex vivo. T. cruzi infections in COX-2 or PGE(2-)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.
Filiaciones:
Guerrero, NA:
CSIC UAM, Ctr Biol Mol Severo Ochoa, Madrid, Spain
Camacho, M:
Hosp Santa Creu & Sant Pau, Inst Recerca, E-08025 Barcelona, Spain
Vila, L:
Hosp Santa Creu & Sant Pau, Inst Recerca, E-08025 Barcelona, Spain
Iniguez, MA:
CSIC UAM, Ctr Biol Mol Severo Ochoa, Madrid, Spain
Inst Invest Sanitaria Princesa, Madrid, Spain
Chillon-Marinas, C:
CSIC UAM, Ctr Biol Mol Severo Ochoa, Madrid, Spain
Cuervo, H:
CSIC UAM, Ctr Biol Mol Severo Ochoa, Madrid, Spain
Columbia Univ, Med Ctr, Dept Obstet Gynecol, New York, NY USA
Poveda, C:
CSIC UAM, Ctr Biol Mol Severo Ochoa, Madrid, Spain
Fresno, M:
CSIC UAM, Ctr Biol Mol Severo Ochoa, Madrid, Spain
Inst Invest Sanitaria Princesa, Madrid, Spain
Girones, N:
CSIC UAM, Ctr Biol Mol Severo Ochoa, Madrid, Spain
Inst Invest Sanitaria Princesa, Madrid, Spain
Green Published, gold, Green Submitted
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