Nitric oxide synthase-2 modulates chemokine production by Trypanosoma cruzi-infected cardiac myocytes

Fabiana S. Machado, Janeusa T. Souto, Marcos A. Rossi, Lisia Esper, Herbert B. Tanowitz, Julio Aliberti, João S. Silva

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

An intense inflammatory process is associated with Trypanosoma cruzi infection. We investigated the mediators that trigger leukocyte activation and migration to the heart of infected mice. It is known that nitric oxide (NO) modulates the inflammatory response. During T. cruzi infection, increased concentrations of NO are produced by cardiac myocytes (CMs) in response to IFN-γ and TNF. Here, we investigated whether NO, IFN-γ and TNF regulate chemokine production by T. cruzi-infected CMs. In addition, we examined the effects of the NOS2 deficiency on chemokine expression both in cultured CMs and in hearts obtained from infected mice. After infection of cultured WT CMs with T. cruzi, the addition of IFN-γ and TNF increased both mRNA and protein levels of the chemokines CXCL1, CXCL2, CCL2, CCL3, CCL4 and CCL5. Interestingly, T. cruzi-infected NOS2-deficient CMs produced significantly higher levels of CCL2, CCL4, CCL5 and CXL2 in the presence of IFN-γ and TNF. Infection of NOS2-null mice resulted in a significant increase in the expression of both chemokine mRNA and protein levels in the heart of, compared with hearts obtained from, infected WT mice. Our data indicate that NOS2 is a potent modulator of chemokine expression which is critical to triggering the generation of the inflammatory infiltrate in the heart during T. cruzi infection.

Original languageEnglish (US)
Pages (from-to)1558-1566
Number of pages9
JournalMicrobes and Infection
Volume10
Issue number14-15
DOIs
StatePublished - Nov 1 2008

Keywords

  • Chemokines
  • Myocarditis
  • Nitric oxide
  • Trypanosoma cruzi

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Infectious Diseases

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    Machado, F. S., Souto, J. T., Rossi, M. A., Esper, L., Tanowitz, H. B., Aliberti, J., & Silva, J. S. (2008). Nitric oxide synthase-2 modulates chemokine production by Trypanosoma cruzi-infected cardiac myocytes. Microbes and Infection, 10(14-15), 1558-1566. https://doi.org/10.1016/j.micinf.2008.09.009