Producción CyT
Artículo
Autoría
Fecha
2010
Editorial y Lugar de Edición
PERGAMON-ELSEVIER SCIENCE LTD
Revista
MOLECULAR IMMUNOLOGY,
vol. 47
(pp. 2485-2491)
PERGAMON-ELSEVIER SCIENCE LTD
Resumen
Información suministrada por el agente en
SIGEVA
Previously, we demonstrated that Benznidazole (BZL), known for its antiparasitic action on T. cruzi, modulates pro-inflammatory cytokines and NO release in macrophages by inhibiting NF-κB. We now proceeded to elucidate the molecular mechanisms by which BZL exerts its inhibitory action on NF-kB. We demonstrated that the inhibitory effect of BZL is not extended to other macrophage responses, since it did not inhibit other typical hallmarks of macrophage activation such as phagocytosis, MHC-...
Previously, we demonstrated that Benznidazole (BZL), known for its antiparasitic action on T. cruzi, modulates pro-inflammatory cytokines and NO release in macrophages by inhibiting NF-κB. We now proceeded to elucidate the molecular mechanisms by which BZL exerts its inhibitory action on NF-kB. We demonstrated that the inhibitory effect of BZL is not extended to other macrophage responses, since it did not inhibit other typical hallmarks of macrophage activation such as phagocytosis, MHC-II molecules expression or production of reactive oxygen species (ROS) by NADPH oxidase. BZL was able to interfere specifically with the activation of NF-kB pathway without affecting AP-1 activation in RAW 264.7 macrophages, not only in LPS-mediated activation, but also for other stimuli, such as pro-inflammatory cytokines (IL-1b, TNF-a), PMA or H2O2. Also, BZL delayed the activation of p38 MAPK, but not that of ERK1/2 and JNK. Finally, treatment with BZL inhibited IkBa phosporylation and hence its degradation, whereas it did not block IkB Kinase (IKK) a/b phosphorylation. Collectively, BZL behaves as a broad range specific inhibitor of NF-kB activation, independently of the stimuli tested.
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Palabras Clave
iNOSNF-kBBenznidazol