The levels of RAC3 expression are up regulated by TNF in the inflammatory response

MARÍA FERNANDA RUBIO; CECILIA VIVIANA ALVARADO; PABLO NICOLAS FERNÁNDEZ LARROSA; LAURA CAROLINA PANELO; PABLO JAVIER AZURMENDI; MARINA RUIZ GRECCO; GISELLE ASTRID MARTÍNEZ NOEL; MÓNICA ALEJANDRA COSTAS

FEBS Open Bio

Elsevier

Lugar: Amsterdam; Año: 2014

2211-5463

RAC3 is a Glucocorticoid Receptor and Nuclear Factor-kB coactivator usually overexpressedin tumors that also has important functions in the immune system. In this work, 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 the RAC3 levels. In mice sub-lethal doses of Lipopolysaccharide induces the increase of RAC3 in spleen while the administration of the synthetic anti-inflammatory glucocorticoid Dexamethasone has a similar effect. However, the simultaneous treatment with bothstimuli is mutually antagonistic. In vitro stimulation of the HEK293 cell line with one of the cytokines induced by Lipopolysaccharide, like Tumor Necrosis Factor also increases the levels of RAC3 mRNA and protein, which correlates with an enhanced transcription dependent of the RAC3 gene promoter. We found that binding of the transcription factor Nuclear Factor-kB to the RAC3 gene promoter could be responsible of these effects. Although glucocorticoid alone has the same effect that Tumor Necrosis Factor, no synergism or antagonism was observed in vitro by simultaneous stimulation.Our results suggest that increase of RAC3 during inflammation or 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.