Role of endogenous IFN- gamma in macrophage programming induced by IL-12 and IL-18 (2006)
- Authors:
- USP affiliated authors: RUSSO, MOMTCHILO - ICB ; MOSIG, JOSE MARIA ALVAREZ - ICB ; LIMA, MARIA REGINA D'IMPERIO - ICB
- Unidade: ICB
- Assunto: IMUNOLOGIA
- Language: Inglês
- Abstract: Introduction and objectives: It is well established that IL-12, in synergism with IL-18, is a potent stimulus for IFN-g production by NK, T and B cells. Yet, the effects of these cytokines on macrophages are largely unknown. Here, we investigated the role of IL-12/IL-18 on nitric oxide (NO) and TNF-a production by CD11b+ adherent peritoneal cells, focusing on the involvement of endogenously produced IFN-g. Methods and results: Cells from C57BL/6 mice released substantial amounts of NO when stimulated with IFN-g or LPS, but failed to respond to IL-12 and/or IL-18. However, IL-12/IL-18 pretreatment was able to program C57BL/6 cells to release 6-8 folds more NO and TNF-a in response to LPS or Trypanosoma cruzi stimulation, with NO levels directly correlating with macrophage resistance to intracellular parasite growth. Analysis of IL-12/IL-18-primed cells from knockout mice revealed that endogenous IFN-g, IFN-gR and IRF-1 were essential for LPS-induced NO release, but TNF-a production was IFN-gindependent.Conversely, the MyD88-dependent pathway was indispensable for IL-12/IL-18- programmed LPS-induced TNF-a production, but not for NO release. Contaminant T and NK cells largely modulated the IL-12/IL-18 programming of LPS-induced NO response through IFNg secretion. Nevertheless, a small population of IFN-g+ cells with a macrophage phenotype was also identified, particularly in the peritoneum of chronically T. cruzi-infected mice, reinforcing thenotion that macrophages can be an alternative source of IFN-g. Conclusion: Taken together, our data contribute to elucidate the molecular basis of the IL-12/IL-18 autocrine pathway of macrophage activation, showing that endogenous IFN-g plays an important role in programming the NO response, whereas the TNF-a response occurs through an IFN-g-independent pathway.
- Imprenta:
- Source:
- Título: Abstracts
- Conference titles: Meeting of the Brazilian Society for Immunology
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ABNT
BASTOS, Karina R B et al. Role of endogenous IFN- gamma in macrophage programming induced by IL-12 and IL-18. 2006, Anais.. São Paulo: Instituto de Ciências Biomédicas, Universidade de São Paulo, 2006. . Acesso em: 18 fev. 2026. -
APA
Bastos, K. R. B., Barboza, R., Sardinha, L., Russo, M., Alvarez, J. M., & Lima, M. R. D. 'I. (2006). Role of endogenous IFN- gamma in macrophage programming induced by IL-12 and IL-18. In Abstracts. São Paulo: Instituto de Ciências Biomédicas, Universidade de São Paulo. -
NLM
Bastos KRB, Barboza R, Sardinha L, Russo M, Alvarez JM, Lima MRD'I. Role of endogenous IFN- gamma in macrophage programming induced by IL-12 and IL-18. Abstracts. 2006 ;[citado 2026 fev. 18 ] -
Vancouver
Bastos KRB, Barboza R, Sardinha L, Russo M, Alvarez JM, Lima MRD'I. Role of endogenous IFN- gamma in macrophage programming induced by IL-12 and IL-18. Abstracts. 2006 ;[citado 2026 fev. 18 ] - The influence of endogenous IFN-g production in autocrine activation and programming of macrophages by IL-12
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