IRIBARREN PABLO
Congresos y reuniones científicas
Título:
Participation of IFN gamma in IL-12 plus IL-18-induced neuroinflammation
Autor/es:
GAVIGLIO, EA; PERALTA RAMOS, JM; ARROYO, DS; BUSSI, C; RODRIGUEZ-GALAN, MC; IRIBARREN, P
Lugar:
Mar del Plata
Reunión:
Congreso; SAI / SAIC; 2014
Institución organizadora:
SAI/SAIC
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, which
could contribute to tissue damage and to induce persistent activation
of MC. Hydrodynamic injection of IL-12 and IL-18 cDNAs has
previously been reported to generate high and persistent systemic
levels of IL-12, IL-18 as well as IFN gamma (IFNg) and TNF alpha
(TNFa) and to induce leukocyte recruitment and activation of MC
in the brain. Since IL-12 and IL-18 were able to induce increased
levels of IFNg and TNFa in mice, we wanted to evaluate the impact
of systemic absence of TNFa or IFNg on the neuroinflammatory
response. Therefore C57BL/6J, TNFa KO and IFNg KO mice were
injected intravenously by hydrodynamic shear with the cDNAs for
IL-12 plus IL-18 or control plasmid. Seven days after injection, mice were sacrificed perfused with HBSS and brains were collected.
Cells suspensions were obtained for analysis of brain inflammatory
cells using flow cytometry. Data demonstrated that the effects of
hydrodynamic injection of IL-12 plus IL-18 were not affected by
the absence of TNFa, however, IFNg deficiency decreased the
number of recruited cells (CD45 high CD11b+) (p<0.05), which
were mainly CD45 high CD11b+ Ly6C+ (p<0.05). Besides, IFNg
KO mice hydrodynamically injected showed reduced levels of MHC
II molecules in both parenchymal MC (CD11b+CD45 low) (p<0.01)
and CD45 high CD11b+(p<0,001) recruited cells, compared with
WT mice. Moreover, in IFNg KO mice the hydrodynamic injection of
IL-12 and IL-18 failed to induce splenomegaly (p>0.05). Systemic
expression of IL-12 and IL-18, in the absence of LPS, induces
leukocyte recruitment to the brain and activation of resident MC.
Interestingly, IFNg seems to participate in monocyte recruitment
into the CNS and activation of resident MC.
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, which
could contribute to tissue damage and to induce persistent activation
of MC. Hydrodynamic injection of IL-12 and IL-18 cDNAs has
previously been reported to generate high and persistent systemic
levels of IL-12, IL-18 as well as IFN gamma (IFNg) and TNF alpha
(TNFa) and to induce leukocyte recruitment and activation of MC
in the brain. Since IL-12 and IL-18 were able to induce increased
levels of IFNg and TNFa in mice, we wanted to evaluate the impact
of systemic absence of TNFa or IFNg on the neuroinflammatory
response. Therefore C57BL/6J, TNFa KO and IFNg KO mice were
injected intravenously by hydrodynamic shear with the cDNAs for
IL-12 plus IL-18 or control plasmid. Seven days after injection, mice were sacrificed perfused with HBSS and brains were collected.
Cells suspensions were obtained for analysis of brain inflammatory
cells using flow cytometry. Data demonstrated that the effects of
hydrodynamic injection of IL-12 plus IL-18 were not affected by
the absence of TNFa, however, IFNg deficiency decreased the
number of recruited cells (CD45 high CD11b+) (p<0.05), which
were mainly CD45 high CD11b+ Ly6C+ (p<0.05). Besides, IFNg
KO mice hydrodynamically injected showed reduced levels of MHC
II molecules in both parenchymal MC (CD11b+CD45 low) (p<0.01)
and CD45 high CD11b+(p<0,001) recruited cells, compared with
WT mice. Moreover, in IFNg KO mice the hydrodynamic injection of
IL-12 and IL-18 failed to induce splenomegaly (p>0.05). Systemic
expression of IL-12 and IL-18, in the absence of LPS, induces
leukocyte recruitment to the brain and activation of resident MC.
Interestingly, IFNg seems to participate in monocyte recruitment
into the CNS and activation of resident MC.
