Role of endothelin receptors in the control of central nervous system parasitism in Trypanosoma cruzi infection in rats

Rachid, Milene A.; Teixeira, Antônio L.; Barcelos, Lucíola S.; Machado, Conceição R.S.; Chiari, Egler; Tanowitz, Herbert B.; Camargos, Elizabeth R.S.; Teixeira, Mauro M.

doi:10.1016/j.jneuroim.2010.01.008

« Previous Next »Journal of Neuroimmunology
Volume 220, Issue 1 , Pages 64-68, 30 March 2010

Role of endothelin receptors in the control of central nervous system parasitism in Trypanosoma cruzi infection in rats

Milene A. Rachid
- Departamento de Patologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), 31270901, Belo Horizonte, MG, Brazil
- Corresponding author. Tel.: +55 31 3409 2649; fax: +55 31 3409 2614.
Antônio L. Teixeira
- Departamento de Bioquímica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), 31270901, Belo Horizonte, MG, Brazil
Lucíola S. Barcelos
- Departamento de Bioquímica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), 31270901, Belo Horizonte, MG, Brazil
Conceição R.S. Machado
- Departamento de Patologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), 31270901, Belo Horizonte, MG, Brazil
Egler Chiari
- Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), 31270901, Belo Horizonte, MG, Brazil
Herbert B. Tanowitz
- Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA
Elizabeth R.S. Camargos
- Departamento de Patologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), 31270901, Belo Horizonte, MG, Brazil
Mauro M. Teixeira
- Departamento de Bioquímica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), 31270901, Belo Horizonte, MG, Brazil

Received 24 August 2009; received in revised form 2 December 2009; accepted 12 January 2010. published online 01 February 2010.

Abstract

Endothelin has been implicated in the pathogenesis of experimental and human Chagas disease. In the present study, we investigated whether the treatment with bosentan, an antagonist of both ET_A/ET_B endothelin receptors, modified parasite load and inflammation in the central nervous system (CNS) of Trypanosoma cruzi-infected rats. The cerebellum was the most affected region in the CNS with marked parasitism and inflammation. Treatment with bosentan enhanced parasitemia and CNS parasitism, but control of infection was eventually attained. There was also an increase in the levels of the cytokines TNF-α, IL-10, IFN-γ, CCL2/MCP-1, CCL3/MIP-1α and CCL5/RANTES in the brain of infected animals at days 9, 13 and 18 after infection. Overall, bosentan has some effects on the expression of certain cytokines and this may be related to the initial enhanced parasite load. Altogether, our data suggest that endothelin action via ET_A and ET_B receptors may play a role in the initial resistance of the CNS to T. cruzi infection in rats.

Keywords: Chagas disease, Endothelin, Central nervous system, Chemokines