IBR   13079
INSTITUTO DE BIOLOGIA MOLECULAR Y CELULAR DE ROSARIO
Unidad Ejecutora - UE
artículos
Título:
Benznidazole blocks NF-kB activation but not AP-1 through inhibition of IKK
Autor/es:
MANARIN ROMINA; PASCUTTI MARÍA FERNANDA; RUFFINO JUAN PABLO; DE LAS HERAS BEATRIZ; BOSCÁ LISARDO; BOTTASSO OSCAR; REVELLI SILVIA; SERRA ESTEBAN
Revista:
MOLECULAR IMMUNOLOGY
Editorial:
PERGAMON-ELSEVIER SCIENCE LTD
Referencias:
Año: 2010 vol. 47 p. 2485 - 2491
ISSN:
0161-5890
Resumen:
Previously, we demonstrated that benznidazole (BZL), known for its
antiparasitic action on Trypanosoma cruzi, modulates pro-inflammatory
cytokines and NO release in macrophages by inhibiting NF-kappaB. We now
proceeded to elucidate the molecular mechanisms by which BZL exerts its
inhibitory action on NF-kappaB. 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-kappaB 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-1beta, TNF-alpha), PMA or H(2)O(2). Also, BZL delayed the
activation of p38 MAPK, but not that of ERK1/2 and JNK. Finally,
treatment with BZL inhibited IkappaBalpha phosporylation and hence its
degradation, whereas it did not block IkappaB kinase (IKK) alpha/beta
phosphorylation. Collectively, BZL behaves as a broad range specific
inhibitor of NF-kappaB activation, independently of the stimuli tested.