TY - JOUR
T1 - Nitric oxide synthase-2 modulates chemokine production by Trypanosoma cruzi-infected cardiac myocytes
AU - Machado, Fabiana S.
AU - Souto, Janeusa T.
AU - Rossi, Marcos A.
AU - Esper, Lisia
AU - Tanowitz, Herbert B.
AU - Aliberti, Julio
AU - Silva, João S.
N1 - Funding Information:
This work was supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and NIH grants AI-052739, AI-076218 and AI-076248 (HBT).
PY - 2008/11
Y1 - 2008/11
N2 - 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.
AB - 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.
KW - Chemokines
KW - Myocarditis
KW - Nitric oxide
KW - Trypanosoma cruzi
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U2 - 10.1016/j.micinf.2008.09.009
DO - 10.1016/j.micinf.2008.09.009
M3 - Article
C2 - 18951994
AN - SCOPUS:56949089972
SN - 1286-4579
VL - 10
SP - 1558
EP - 1566
JO - Microbes and Infection
JF - Microbes and Infection
IS - 14-15
ER -