Lipoxin A4 impairment of apoptotic signaling in macrophages: Implication of the PI3K/Akt and the ERK/Nrf-2 defense pathways

P. Prieto, J. Cuenca, P. G. Través, M. Fernández-Velasco, P. Martín-Sanz, L. Boscá

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva

60 Citas (Scopus)

Resumen

Lipoxin A4 (LXA4) is an endogenous lipid mediator that requires transcellular metabolic traffic for its synthesis. The targets of LXA4 on neutrophils are well described, contributing to attenuation of inflammation. However, effects of lipoxins on macrophage are less known, particularly the action of LXA4 on the regulation of apoptosis of these cells. Our data show that pretreatment of human or murine macrophages with LXA4 at the concentrations prevailing in the course of resolution of inflammation (nanomolar range) significantly inhibits the apoptosis induced by staurosporine, etoposide and S-nitrosoglutathione or by more pathophysiological stimuli, such as LPS/IFNγ challenge. The release of mitochondrial mediators of apoptosis and the activation of caspases was abrogated in the presence of LXA4. In addition to this, the synthesis of reactive oxygen species induced by staurosporine was attenuated and antiapoptotic proteins of the Bcl-2 family accumulated in the presence of lipoxin. Analysis of the targets of LXA4 identified an early activation of the PI3K/Akt and ERK/Nrf-2 pathways, which was required for the observation of the antiapoptotic effects of LXA4. These data suggest that the LXA 4, released after the recruitment of neutrophils to sites of inflammation, exerts a protective effect on macrophage viability that might contribute to a better resolution of inflammation.
Idioma originalInglés estadounidense
Páginas (desde-hasta)1179-1188
Número de páginas10
PublicaciónCell Death and Differentiation
Volumen17
N.º7
DOI
EstadoPublicada - 1 jul 2010
Publicado de forma externa

Palabras clave

  • Lipoxin
  • Macrophage
  • Nrf2
  • Oxidative stress

Huella Profundice en los temas de investigación de 'Lipoxin A<sub>4</sub> impairment of apoptotic signaling in macrophages: Implication of the PI3K/Akt and the ERK/Nrf-2 defense pathways'. En conjunto forman una huella única.

Citar esto