info:eu-repo/semantics/article
The levels of RAC3 expression are up regulated by TNF in the inflammatory response
Fecha
2014-01Registro en:
Alvarado, Cecilia Viviana; Rubio, Maria Fernanda; Fernández Larrosa, Pablo Nicolás; Panelo, Laura Carolina; Azurmendi, Pablo Javier; et al.; The levels of RAC3 expression are up regulated by TNF in the inflammatory response; Wiley; Febs Open Bio; 4; 1; 1-2014; 450-457
2211-5463
CONICET Digital
CONICET
Autor
Alvarado, Cecilia Viviana
Rubio, Maria Fernanda
Fernández Larrosa, Pablo Nicolás
Panelo, Laura Carolina
Azurmendi, Pablo Javier
Ruiz Grecco, Marina
Martínez Noël, Giselle María Astrid
Costas, Monica Alejandra
Resumen
RAC3 is a coactivator of glucocorticoid receptor and nuclear factor-κB (NF-κB) that is usually over-expressed in tumors and which also has important functions in the immune system. We investigated the role of the inflammatory response in the control of RAC3 expression levels in vivo and in vitro. We found that inflammation regulates RAC3 levels. In mice, sub-lethal doses of lipopolysaccharide induce the increase of RAC3 in spleen and the administration of the synthetic anti-inflammatory glucocorticoid dexamethasone has a similar effect. However, the simultaneous treatment with both stimuli is mutually antagonistic. In vitro stimulation of the HEK293 cell line with tumor necrosis factor (TNF), one of the cytokines induced by lipopolysaccharide, also increases the levels of RAC3 mRNA and protein, which correlates with an enhanced transcription dependent on the RAC3 gene promoter. We found that binding of the transcription factor NF-κB to the RAC3 gene promoter could be responsible for these effects. Although glucocorticoid alone has the same effect that TNF, no synergism or antagonism was observed in vitro by simultaneous stimulation. Our results suggest that increase of RAC3 during inflammation or an anti-inflammatory response could be a molecular mechanism involved in the control of sensitivity to both stimuli in order to maintain the normal healthy course of the immune response.