IRIBARREN PABLO
Congresos y reuniones científicas
Título:
Interleukin 12 and Interleukin 18 gene administration induces leukocyte recruitment and activation of microglia in the brain
Autor/es:
RODRIGUEZ-GALAN, MC; GAVIGLIO, EA; SORIA, JA; BARRIOS, B; ARROYO, DS; IRIBARREN, P
Reunión:
Congreso; 8th WORLD CONGRESS OF IBRO; 2011
Resumen:
Microglial cells (MC) are key immune cells within the central nervous system (CNS). They participate in CNS homeostasis and become activated once they contact pro-inflammatory signals. Some CNS injuries are accompanied by cell infiltration. The recruitment of inflammatory cells could contribute to tissue damage and to induce persistent activation of MC.
Systemic administration of bacterial lipopolysaccharide (LPS), which generates a systemic pro-inflammatory cytokines storm, induces brain inflammation and leukocyte recruitment to the CNS.
Here, we evaluated the impact of hydrodynamic injection of expression vectors (naked cDNA) encoding for the cytokines IL-12 and IL-18, on brain MC activation and leukocyte recruitment. Hydrodynamic injection of IL-12 and IL-18 cDNAs has previously been reported to induce high and persistent systemic levels of IL-12, IL-18 as well as IFNgamma and TNFalpha
C57BL6 mice were injected intravenously by hydrodynamic shear with the cDNAs for IL-12 alone, IL-12 plus IL-18 or the control plasmid. Seven days after the injections, mice were sacrificed perfussed with HBSS and brains were collected. Cells suspensions were obtained for brain inflammatory cells analysis using four color flow cytometry.
Data demonstrated that both, IL-12 alone and IL-12 plus IL-18 cDNA expression induced recruitment of leukocytes (p<0.05). In addition, we observed that infiltrating CD11b+ CD45high cells expressed increased levels of major hystocompatibility complex class II (MHCII) molecules indicating cell activation. Moreover, co-expression of IL-12 and IL-18 induced increased levels of MHCII molecules on parenchymal CD11b+CD45low MC.
These results suggest that systemic expression of IL-12 and IL-18, in the absence of LPS, induces activated leukocyte infiltration into the brain and activation of resident MC.
Systemic administration of bacterial lipopolysaccharide (LPS), which generates a systemic pro-inflammatory cytokines storm, induces brain inflammation and leukocyte recruitment to the CNS.
Here, we evaluated the impact of hydrodynamic injection of expression vectors (naked cDNA) encoding for the cytokines IL-12 and IL-18, on brain MC activation and leukocyte recruitment. Hydrodynamic injection of IL-12 and IL-18 cDNAs has previously been reported to induce high and persistent systemic levels of IL-12, IL-18 as well as IFNgamma and TNFalpha
C57BL6 mice were injected intravenously by hydrodynamic shear with the cDNAs for IL-12 alone, IL-12 plus IL-18 or the control plasmid. Seven days after the injections, mice were sacrificed perfussed with HBSS and brains were collected. Cells suspensions were obtained for brain inflammatory cells analysis using four color flow cytometry.
Data demonstrated that both, IL-12 alone and IL-12 plus IL-18 cDNA expression induced recruitment of leukocytes (p<0.05). In addition, we observed that infiltrating CD11b+ CD45high cells expressed increased levels of major hystocompatibility complex class II (MHCII) molecules indicating cell activation. Moreover, co-expression of IL-12 and IL-18 induced increased levels of MHCII molecules on parenchymal CD11b+CD45low MC.
These results suggest that systemic expression of IL-12 and IL-18, in the absence of LPS, induces activated leukocyte infiltration into the brain and activation of resident MC.
