CDM exhibits immunomodulatory and antiangiogenic effects without affecting NF-kB and p38 MAPK pathways

BUENO CARLOS; BARQUERO ANDREA; MAIER MARTA; ALCHÉ LAURA

Los Cocos, Córdoba

Simposio; The First South American Spring Symposium in Signal Transduction and Molecular Medicine (SISTAM 2010); 2010

The antiviral limonoid 1-cinnamoyl-3,11-dihydroxymeliacarpin (CDM) modulates IL-6 and TNF-α production in macrophages stimulated with LPS or infected with HSV-1. CDM inhibits the vascular endotelial growth factor (VEGF) transcription as a consequence of the reduction of IL-6 level, but it does not prevent NF-kB translocation in LPS stimulated-macrophages.These findings suggest that CDM could be affecting NF-kB activation or an alternative cell signaling pathway involved in the production of cytokines.Our studies showed that CDM did not impede NF-kB activation when macrophages were transfected with a NF-kB-luciferase reporter plasmid and phosphorylation of p38 MAPK by Western blotting.Considering that CDM inhibits the transcription of VEGF, we analized the antiangiogenic properties of CDM on Human umbilical vein endothelial cell (HUVEC) formation of capillary-like tubes. CDM led to a drastic reduction in the number of capillary-like structures formation in a dose-dependent manner. In addition, this inhibition of HUVEC angiogenesis by CDM seemed to be a consequence of the modulation of IL-6 and TNF-α secretion.We conclude that the antiangiogenic activity of CDM would be a consequence of its immunomodulatory activity, affecting an alternative NF-κB and p38 MAPK cell signaling pathway.