Effects of erythropoietin upon activation of microglial cells and neuronal damage induced by proinflammatory environment

WENKER, S; CHAMORRO, ME; VITTORI, D; NESSE, A

Buenos Aires

Simposio; 2do. SIMPOSIO FRANCO-ARGENTINO DE NEUROCIENCIAS; 2012

LIA DEVENIR: Laboratorio Internacional Asociado para el Desarrollo de Vectores Neurotropicos para la Investigacion en Neurociencias - (CNRS / Univ. Lyon1 y CONICET / UBA)

Effects of erythropoietin upon activation of microglial cells and neuronal damage induced by proinflammatory environment Shirley D. Wenker, María E. Chamorro, Daniela C. Vittori #, Alcira B. Nesse # * Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, IQUIBICEN-CONICET (Consejo Nacional de Investigaciones Científicas y Técnicas), Argentina ABSTRACT Inflammation is a physiological response of defense but may also represent a potential pathological process in neurological diseases. In this regards, microglia have a crucial role upon either progression or amelioration of degenerative neuronal damage. Because of the role of hypoxia in proinflammatory mechanisms in the nervous system, and the antiinflammatory protective effect of erythropoietin (Epo), we focused our investigation on the role of this factor upon activation of microglia and in neuroprotection. Activation of microglial cells (EOC-2) was achieved by exposure to CoCl2-induced chemical hypoxia. Under this condition, proinflammatory mediators such as nitrites and TNF- increased, ROS production was high, and iNOS expression was upregulated while cell proliferation data and PCNA stain demonstrated the mitogenic effect of chemical hypoxia. The results shows that pretreatment with Epo was unable to change nitrite production, iNOS protein expression or TNF- secretion. Interestingly, Epo prevented the reactive oxygen species generation upon activated EOC-2 microglial cells. On the other hand, conditioned media from activated microglial cells induced apoptosis of SH-SY5Y neuronal cells, effect that was abolished by Epo. Therefore, in addition to its antiapoptotic action, this antioxidant ability of Epo might account for its effect upon neuronal cells since Epo did increase the resistance of neurons to the subsequent damage derived from the proinflammatory function of microglial cells. The results show that even though Epo did not exert a direct antiinflammatory effect upon microglial activation, it did increase the resistance of neurons to subsequent damage derived from microglial cell function. Therefore, in addition to the Epo antiapoptotic ability, its antioxidant effect might account for the observed neuroprotective action.