IRIBARREN PABLO
Congresos y reuniones científicas
Título:
IL4 REGULATES ACTIVATION OF PEPTIDOGLYCAN-STIMULATED MICROGLIAL CELLS
Autor/es:
ARROYO, DS; GAVIGLIO, EA; SORIA, JA; IRIBARREN, P
Lugar:
Buenos Aires
Reunión:
Congreso; First French-Argentine Immunology Congress; 2010
Institución organizadora:
Sociedad Argentina de Inmunología
Resumen:

Microglial cells (MC) are involved in responses of the central nervous system (CNS) against infections, aseptic inflammation, injury and neurodegeneration. These cells are accumulated at sites of injury and have the capability of activating when they contact either with endogenous or exogenous signals (pathogens). Our preliminary studies have shown that after prolonged stimulation of MC with peptidoglycan of Staphylococcus aureus (PGN, TLR2 agonist) several neurotoxic factors (IL1b, TNFa, IL6 and nitric oxide (NO)) are produced. IL4 is a cytokine with diverse biological activities, including the induction of alternative activation in macrophages and the inhibition of LPS-induced TLR4 signaling cascade in macrophages and MC. Thus, IL4 may participate in the homeostasis of the CNS by controlling MC responses to inflammatory stimulants.

Here, our aim was to study the capacity of IL4 to modulate the PGN-stimulated activation and survival of MC. We first examined (by intracellular flow cytometry and Griess? reaction) the effects of IL-4 on the pro-inflammatory mediators production in PGN-stimulated MC line BV2. We found that PGN and Pam3CSK4 (another TLR2 ligand) increased TNFa and NO production (Medium 0,023 ± 0,041; PGN 1,992 ± 0,170; Pam3CSK4 1,864 ± 0,325; p<0.05). In contrast, IL-4 was able to reduce TNFa and NO production in these cells (IL4 0,069 ± 0,079; IL4+PGN 0,496 ± 0,216; IL4+Pam3CSK4 0,940 ± 0,269 p<0.05). In another set of experiments we found that prolonged stimulation of MC with PGN induced cell death (Annexin V /7AAD staining) and the effect was enhanced by pretreatment of the cells with IL-4 (statistical significance is currently tested).

These preliminary results suggest that IL4 may regulate potentially harmful responses of PGN-stimulated MC by controlling the production of pro-inflammatory cytokines and reducing the cell number.