TY - JOUR
T1 - Blockade of endothelin ETA/ETB receptors favors a role for endothelin during acute Trypanosoma cruzi infection in rats
AU - Rachid, Milene A.
AU - Camargos, Elizabeth R.S.
AU - Barcellos, Lucíola
AU - Marques, Cecília A.
AU - Chiari, Egler
AU - Huang, Huan
AU - Tanowitz, Hebert B.
AU - Teixeira, Mauro M.
AU - Machado, Conceição R.S.
N1 - Funding Information:
We thank Professor Fernando Q. Cunha for his help in performing the NOx determinations. Supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundação de Amparo a Pesquisa de Minas Gerais (FAPEMIG, PRONEX-MG, 2190-03 and CBB801-03); and NIH Grants (FIRCA Award—RO3 TW006857, AI-12770, AI-052739 and HL-073732).
PY - 2006/7
Y1 - 2006/7
N2 - Endothelin has been implicated in the pathogenesis of experimental and human Chagas' disease (American trypanosomiasis). In the present study, we tested the effect of bosentan, an antagonist of both ETA and ETB endothelin receptors, on parasitemia, histopathology (heart and diaphragm), heart levels of tumor necrosis factor (TNF)-α, interleukin (IL)-10, interferon (IFN)-γ, CCL2, CCL3 and CCL5, and the serum levels of nitrate/nitrite (NOx). Bosentan treatment was accompanied by a significant increase in parasitemia and tissue parasitism or inflammation. In vehicle-treated rats, Trypanosoma cruzi infection increased the cardiac levels of TNF-α, IFN-γ and IL-10, at day 9 post inoculation, and the TNF-α remained elevated until day 13. The infection also caused a significant increase in the cardiac levels of the chemokines CCL2 (9, 13 and 18 days) and CCL3 (13 and 18 days). Bosentan-treatment had no significant effect on the infection-associated increase in IFN-γ and chemokine concentrations. There was a lower increase in IL-10 at day 9 and this was mirrored by a greater increase of TNF-α at day 13, in comparison with vehicle-treated rats. These latter findings correlated well with the enhanced inflammatory process in hearts of bosentan-treated infected rats. Bosentan treatment reduced the infection-associated increase in NOx serum concentration. Altogether, our data suggest that ET action on ETA and ETB receptors may play a role in the initial control of T. cruzi infection in rats probably by interfering in NO production.
AB - Endothelin has been implicated in the pathogenesis of experimental and human Chagas' disease (American trypanosomiasis). In the present study, we tested the effect of bosentan, an antagonist of both ETA and ETB endothelin receptors, on parasitemia, histopathology (heart and diaphragm), heart levels of tumor necrosis factor (TNF)-α, interleukin (IL)-10, interferon (IFN)-γ, CCL2, CCL3 and CCL5, and the serum levels of nitrate/nitrite (NOx). Bosentan treatment was accompanied by a significant increase in parasitemia and tissue parasitism or inflammation. In vehicle-treated rats, Trypanosoma cruzi infection increased the cardiac levels of TNF-α, IFN-γ and IL-10, at day 9 post inoculation, and the TNF-α remained elevated until day 13. The infection also caused a significant increase in the cardiac levels of the chemokines CCL2 (9, 13 and 18 days) and CCL3 (13 and 18 days). Bosentan-treatment had no significant effect on the infection-associated increase in IFN-γ and chemokine concentrations. There was a lower increase in IL-10 at day 9 and this was mirrored by a greater increase of TNF-α at day 13, in comparison with vehicle-treated rats. These latter findings correlated well with the enhanced inflammatory process in hearts of bosentan-treated infected rats. Bosentan treatment reduced the infection-associated increase in NOx serum concentration. Altogether, our data suggest that ET action on ETA and ETB receptors may play a role in the initial control of T. cruzi infection in rats probably by interfering in NO production.
KW - Chagas' disease
KW - Chemokines
KW - Cytokines
KW - Endothelin
KW - Nitric oxide
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U2 - 10.1016/j.micinf.2006.03.017
DO - 10.1016/j.micinf.2006.03.017
M3 - Article
C2 - 16844401
AN - SCOPUS:33748176818
SN - 1286-4579
VL - 8
SP - 2113
EP - 2119
JO - Microbes and Infection
JF - Microbes and Infection
IS - 8
ER -