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

Guerrero NA, Camacho M, Vila L, Íñiguez MA, Chillón-Marinas C, Cuervo H, Poveda C, Fresno M, Gironès N - PLoS Negl Trop Dis (2015)

Bottom Line: Our results show an increase in the expression of several of these enzymes in acute T. cruzi infected heart.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.

View Article: PubMed Central - PubMed

Affiliation: Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Madrid, Spain.

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.

No MeSH data available.


Related in: MedlinePlus

Gene expression of cell markers, chemokines, cytokines and inflammatory enzymes during T. cruzi infection in the heart of COX-2+/+ and COX-2-/- mice.mRNA levels of the different genes analyzed was determined by qRT-PCR in heart tissue RNA samples isolated from non-infected (0 d.p.i.) or 14 d.p.i. COX-2+/+ or COX-2-/- mice. Data are expressed as RQ calculated from CT values as described in Methods. Gene expression of lymphoid and myeloid cell markers as Ptprc, Cd4, Cd8a, Cd68 and Itgax (A), chemokines as Ccl2, Ccl5 and Cxcl9 (B), cytokines as Ifng, Tnf, Il4, Il6 and Il10 (C) and enzymes as Arg1, Nos2, Ptgs1 and Ptges (mPGES1) (D) is shown. Means ± SEM from one representative experiment (n = 3) out of four is shown (n = 5; * p<0.05; **p<0.01; ***p<0.001).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4549243&req=5

pntd.0004025.g004: Gene expression of cell markers, chemokines, cytokines and inflammatory enzymes during T. cruzi infection in the heart of COX-2+/+ and COX-2-/- mice.mRNA levels of the different genes analyzed was determined by qRT-PCR in heart tissue RNA samples isolated from non-infected (0 d.p.i.) or 14 d.p.i. COX-2+/+ or COX-2-/- mice. Data are expressed as RQ calculated from CT values as described in Methods. Gene expression of lymphoid and myeloid cell markers as Ptprc, Cd4, Cd8a, Cd68 and Itgax (A), chemokines as Ccl2, Ccl5 and Cxcl9 (B), cytokines as Ifng, Tnf, Il4, Il6 and Il10 (C) and enzymes as Arg1, Nos2, Ptgs1 and Ptges (mPGES1) (D) is shown. Means ± SEM from one representative experiment (n = 3) out of four is shown (n = 5; * p<0.05; **p<0.01; ***p<0.001).

Mentions: We next analyzed the cellular composition of the immune inflammatory infiltrate by determining gene expression of surface markers characteristic of various immune cell populations by qRT-PCR and normalizing the data from infected animals respect to non-infected controls. In agreement with histological findings, infection in COX-2-/- mice compared to COX-2+/+ mice, led to lower expression of the common leukocyte marker Ptprc (CD45) as well as of Cd4, Cd8, Cd68, and Itgax (CD11c) as markers of T helper cells, cytotoxic T cells, macrophages and dendritic cells, respectively (Fig 4A).


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

Guerrero NA, Camacho M, Vila L, Íñiguez MA, Chillón-Marinas C, Cuervo H, Poveda C, Fresno M, Gironès N - PLoS Negl Trop Dis (2015)

Gene expression of cell markers, chemokines, cytokines and inflammatory enzymes during T. cruzi infection in the heart of COX-2+/+ and COX-2-/- mice.mRNA levels of the different genes analyzed was determined by qRT-PCR in heart tissue RNA samples isolated from non-infected (0 d.p.i.) or 14 d.p.i. COX-2+/+ or COX-2-/- mice. Data are expressed as RQ calculated from CT values as described in Methods. Gene expression of lymphoid and myeloid cell markers as Ptprc, Cd4, Cd8a, Cd68 and Itgax (A), chemokines as Ccl2, Ccl5 and Cxcl9 (B), cytokines as Ifng, Tnf, Il4, Il6 and Il10 (C) and enzymes as Arg1, Nos2, Ptgs1 and Ptges (mPGES1) (D) is shown. Means ± SEM from one representative experiment (n = 3) out of four is shown (n = 5; * p<0.05; **p<0.01; ***p<0.001).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4549243&req=5

pntd.0004025.g004: Gene expression of cell markers, chemokines, cytokines and inflammatory enzymes during T. cruzi infection in the heart of COX-2+/+ and COX-2-/- mice.mRNA levels of the different genes analyzed was determined by qRT-PCR in heart tissue RNA samples isolated from non-infected (0 d.p.i.) or 14 d.p.i. COX-2+/+ or COX-2-/- mice. Data are expressed as RQ calculated from CT values as described in Methods. Gene expression of lymphoid and myeloid cell markers as Ptprc, Cd4, Cd8a, Cd68 and Itgax (A), chemokines as Ccl2, Ccl5 and Cxcl9 (B), cytokines as Ifng, Tnf, Il4, Il6 and Il10 (C) and enzymes as Arg1, Nos2, Ptgs1 and Ptges (mPGES1) (D) is shown. Means ± SEM from one representative experiment (n = 3) out of four is shown (n = 5; * p<0.05; **p<0.01; ***p<0.001).
Mentions: We next analyzed the cellular composition of the immune inflammatory infiltrate by determining gene expression of surface markers characteristic of various immune cell populations by qRT-PCR and normalizing the data from infected animals respect to non-infected controls. In agreement with histological findings, infection in COX-2-/- mice compared to COX-2+/+ mice, led to lower expression of the common leukocyte marker Ptprc (CD45) as well as of Cd4, Cd8, Cd68, and Itgax (CD11c) as markers of T helper cells, cytotoxic T cells, macrophages and dendritic cells, respectively (Fig 4A).

Bottom Line: Our results show an increase in the expression of several of these enzymes in acute T. cruzi infected heart.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.

View Article: PubMed Central - PubMed

Affiliation: Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Madrid, Spain.

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.

No MeSH data available.


Related in: MedlinePlus