Cyclooxygenase-2 and Prostaglandin E2 Signaling through Prostaglandin Receptor EP-2 Favor the Development of Myocarditis during Acute Trypanosoma cruzi Infection

Guerrero, Néstor; Camacho, Mercedes; Vilá, Luis M.; Íñiguez, Miguel A.; Chillón-Marinas, Carlos; Cuervo, Henar; Poveda, Cristina; Fresno, Manuel; Gironès, Núria

doi:10.1371/journal.pntd.0004025

Cited by 26 publications

(22 citation statements)

References 59 publications

(70 reference statements)

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“…Recent evidence suggests a role of COX-2 and PGE 2 signaling through EP-2 receptor in the development of myocarditis during acute T. cruzi infection in mice. In fact, it was showed a marked reduction in the cardiac inflammatory infiltration in knockout mice deficient in the expression of COX-2 (COX-2 −/− ) and the prostaglandin PGE 2 receptor EP-2 (EP-2 −/− ) infected with T. cruzi compared to infected wild type animals (Guerrero et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Response to Trypanosoma cruzi by Human Blood Cells Enriched with Dentritic Cells Is Controlled by Cyclooxygenase-2 Pathway

et al. 2017

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Chagas disease (Cd) or American human trypanosomiasis is caused by Trypanosoma cruzi and affects ~7 million people, mostly in Latin America. The infective trypomastigote forms of the parasite can invade several human blood cell populations, including monocytes and dendritic cells (DC). Although these cells display a wide functional diversity, their interactions with T. cruzi via cyclooxygenase (COX) and cyclic adenosine monophosphate (cAMP) dependent pathways have not been analyzed. To exploiting this mechanism, DC-enriched peripheral human blood mononuclear cell populations (DC-PBMC) were used as our model. Our results showed that the treatment of these cell populations with celecoxib (CEL), a cyclooxygenase-2 selective inhibitor or SQ 22,536, an adenilate cyclase inhibitor, significantly caused marked inhibition of T. cruzi infection. In contrast, aspirin (ASA, a non-selective COX-1 and COX-2 inhibitor) treatment did not inhibit the infection of the cells by the parasite and was independent of nitric oxide (NO) production. The expression of co-stimulatory molecules CD80 and CD86 were similar on cells treated or not with both COX-inhibitors. The infection stimulated the release of TNF-α, IL-1β, IL-6, IL-8, and IL-10 production by infected cells. Treatment with ASA or CEL did not affect TNF-α, IL-6, IL-8, IL-10, and NO production by infected cells, but increased IL-1β production by them. Our results suggest a key role of COX-2 and cAMP pathways in T. cruzi invasion process of human blood cells and these pathways may represent targets of new therapeutic options for Cd.

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Section: Discussionmentioning

confidence: 99%

Response to Trypanosoma cruzi by Human Blood Cells Enriched with Dentritic Cells Is Controlled by Cyclooxygenase-2 Pathway

et al. 2017

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“…As previously described [ 22 ], hearts were collected from mice at 14 d.p.i. and placed in 10% neutral buffered formalin for at least 4 h at room temperature, followed by incubation in 70% ethanol overnight.…”

Section: Methodsmentioning

confidence: 99%

L-arginine supplementation reduces mortality and improves disease outcome in mice infected with Trypanosoma cruzi

et al. 2018

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Chagas disease caused by Trypanosoma cruzi is a neglected disease that affects about 7 million people in Latin America, recently emerging on other continents due to migration. As infection in mice is characterized by depletion of plasma L-arginine, the effect on infection outcome was tested in mice with or without L-arginine supplementation and treatment with 1400W, a specific inhibitor of inducible nitric oxide synthase (iNOS). We found that levels of L-arginine and citrulline were reduced in the heart and plasma of infected mice, whereas levels of asymmetric dimethylarginine, an endogenous iNOS inhibitor, were higher. Moreover, L-arginine supplementation decreased parasitemia and heart parasite burden, improving clinical score and survival. Nitric oxide production in heart tissue and plasma was increased by L-arginine supplementation, while pharmacological inhibition of iNOS yielded an increase in parasitemia and worse clinical score. Interestingly, electrocardiograms improved in mice supplemented with L-arginine, suggesting that it modulates infection and heart function and is thus a potential biomarker of pathology. More importantly, L-arginine may be useful for treating T. cruzi infection, either alone or in combination with other antiparasitic drugs. Author summaryTrypanosoma cruzi is the causative agent of the neglected Chagas disease in humans. During infection in mice, depletion of plasma L-arginine is correlated with mortality. L-arginine is a semi-essential amino acid needed for cell proliferation, and is the substrate of arginase 1 (Arg-1) and inducible nitric oxide synthase (iNOS), which is involved in the immune response against infections. Observed L-arginine depletion is likely caused by increased Arg-1 activity, but the effect on immune response are still unknown. Our PLOS Neglected Tropical Diseases | https://doi

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“…Acute T. cruzi infection in murine models is characterized by cardiac lesions associated by high levels of PGE 2 [51]. During acute T. cruzi infection, both PGE 2 and its EP-2 receptor are involved in inflammation and cardiac inflammatory infiltrate [52], as leukotrienes, that is important for the local production of NO and cardiac parasitism control [53,54]. Additionally, plasma PGE 2 , TBX 2 e 6-oxo-PGF 1α levels are increased in murine models of acute infection [55,56].…”

Section: Long Chain N-3 Pufas and Trypanosoma Cruzi Infectionmentioning

confidence: 99%

Fish Oil and Inflammation: A Perspective on the Challenges of Evaluating Efficacy inTrypanosoma cruziInfection

Lovo‐Martins¹,

Martins‐Pinge²,

Pinge‐Filho³

2019

Biology OfTrypanosoma Cruzi

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Parasitic diseases constitute a big problem of ill health in both the tropics and subtropics as well as in more temperate climates and have been targeted by the Centers for Disease Control and Prevention (CDC) as priorities for public health in the USA. Parasitic infections can be caused by three types of organisms: protozoa, helminths and ectoparasites. They subsist on the host's nutrients at the host's expense. Effectively combating infections caused by parasites is essential for the survival of the organism. In this effort, cells and molecules of the immune system are susceptible to the modulating influence of fatty acids. The primary purpose of this chapter is to present a critical review of the multiple effects of fish-oil on Trypanosoma infection.

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Cyclooxygenase-2 and Prostaglandin E2 Signaling through Prostaglandin Receptor EP-2 Favor the Development of Myocarditis during Acute Trypanosoma cruzi Infection

Cited by 26 publications

References 59 publications

Response to Trypanosoma cruzi by Human Blood Cells Enriched with Dentritic Cells Is Controlled by Cyclooxygenase-2 Pathway

Response to Trypanosoma cruzi by Human Blood Cells Enriched with Dentritic Cells Is Controlled by Cyclooxygenase-2 Pathway

L-arginine supplementation reduces mortality and improves disease outcome in mice infected with Trypanosoma cruzi

Fish Oil and Inflammation: A Perspective on the Challenges of Evaluating Efficacy inTrypanosoma cruziInfection

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