Cyclooxygenase-2 and Prostaglandin E2 Signaling through Prostaglandin Receptor EP-2 Favor the Development of Myocarditis during Acute Trypanosoma cruzi Infection
Entity
UAM. Departamento de Biología MolecularPublisher
Herbert B. Tanowitz; Public Library of ScienceDate
2015-08-25Citation
10.1371/journal.pntd.0004025
PLoS Neglected Tropical Diseases. 9.8 (2015): e0004025
ISSN
1935-2727 (print); 1935-2735 (online)DOI
10.1371/journal.pntd.0004025Funded by
This work was supported by (NG) grants from “Fondo de Investigaciones Sanitarias” (PS09/00538 and PI12/00289); “Universidad Autónoma de Madrid” and “Comunidad de Madrid” (CC08-UAM/SAL-4440/08); by (MF) grants from “Ministerio de Ciencia e Innovación” (SAF2010-17833); “Red de Investigación de Centros de Enfermedades Tropicales” (RICET RD12/0018/0004); European Union (HEALTH-FE-2008-22303, ChagasEpiNet);AECID Cooperation with Argentine (A/025417/09 and A/031735/10), Comunidad de Madrid (S-2010/BMD-2332) and “Fundación Ramón Areces”. NAG was recipient of a ISCIII Ph.D. fellowship financed by the Spanish “Ministerio de Sanidad”. CCM and HC were recipients of contracts from SAF2010-17833 and PI060388, respectively. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscriptProject
Gobierno de España. SAF2010-17833; info:eu-repo/grantAgreement/EC/FP7/223034; Comunidad de Madrid. S2010/BMD-2332/INDISNETEditor's Version
http://dx.doi.org/10.1371/journal.pntd.0004025Subjects
Animal cell; Gene expression; Chagas disease; Cell isolation; Biología y Biomedicina / BiologíaRights
© 2015 Guerrero et alAbstract
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
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Google Scholar:Guerrero, N.
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Camacho, M.
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Vila, L.
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Íñiguez Peña, Miguel Ángel
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Chillón-Marinas, C.
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Cuervo, H.
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Poveda, C.
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Fresno Escudero, Manuel
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Gironés Pujol, Nuria
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