Differential regulation of IGF-1 production in Microglial Cells stimulated with IL-4 or IFN gamma.

EMILIA A GAVIGLIO; JAVIER MARIA PERALTA RAMOS; DANIELA S ARROYO; CLAUDIO BUSSI; MARIA C RODRIGUEZ GALAN; PABLO IRIBARREN

Congreso; LXI REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA; 2013

Insulin like growth factor-1 (IGF-1) is involved in the regulation of growth and tissue differentiation in various organs, including the brain. This factor is synthesised by hepatocytes and released at blood flow or it is produced by muscular and neural cells. In the brain, IGF-1 is one of the most important neurotrophic factors involved in neural cell survival, proliferation and differentiation and it has been related to neuroprotective functions. Microglial cells (MC) are phagocytic myeloid cells located in the nervous parenchyma that have a key immune role in the initiation, progression and resolution of neuroinflammation. When activated, they can perform many diverse functions which may be either beneficial or harmful depending on the stimuli. Therefore, the aim of this study was to determine in vitro if MC were capable of producing IGF-1 and if this production was regulated by IFN gamma (type 1 cytokine) or IL-4 (type 2 cytokine). First of all, we evaluated by real time PCR the effects of the stimulation of murine MC lines with IL-4 or INF gamma, on the expression of the gene coding for IGF-1. IL-4 dose-dependently increased IGF-1 gene expression from 6h to 48h after stimulation (p<0,0001). On the other hand, IFN gamma decreased IGF-1 gene expression in MC and this response was time-dependent (p<0,001). Then we evaluated the production of IGF-1 by ELISA, and we observed that IL-4 increased IGF-1 levels in MC at 24h (p<0,01) whereas IFN gamma induced a decrease in the IGF-1 secretion (p<0,01). Finally, we observed that IL-4 was able to modulate the IGF-1 gene expression on IFN gamma-stimulated MC. We are performing additional experiments to evaluate the effects of supernatants from MC stimulated with IL-4 or IFN gamma, on neuronal cell differentiation and survival. Overall, these preliminary results suggest that type 1 and 2 cytokines are effective modulators of IGF-1 production by MC, which may be important in the regulation of neurodegenerative diseases.