IL4 REGULATES ACTIVATION OF PEPTIDOGLYCAN-STIMULATED MICROGLIAL CELLS

ARROYO, DS; GAVIGLIO, EA ;SORIA, JA; RODRIGUEZ-GALÁN, MC E IRIBARREN, P

Buenos Aires

Congreso; First French-Argentine Immunology Congress; 2010

IL4 REGULATES ACTIVATION OF PEPTIDOGLYCAN-STIMULATED MICROGLIAL CELLS 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 in MC with peptidoglycan of Staphylococcus aureus (PGN, TLR2 agonist) several neurotoxic factors (IL1beta, TNFalfa, IL6 and nitric oxide (NO)) are produced and death of MC are induced. IL4 is a cytokine with diverse biological activities, including converts macrophages to state of alternative activation and suppresses the LPS-induced TLR4 signaling cascade in MC. Thus, IL4 may participate in the homeostasis of the CNS by controlling MC responses to inflammatory stimulants. Our main aim was to study the capacity of IL4 to modulate activation of PGN-stimulated microglia. We found that IL4 reduced TNFalfa production in MC after stimulation with PGN. The study in CM BV2 treated with PGN shown the presence of double positive cell staining with AnnexinV/7AAD and low levels of early apoptotic cells (AnnexinV+), suggesting the presence of necrosis. In addition, BV2 cells incubated with IL4, followed by addition of PGN shown the increases of the death cell. These preliminary results suggest that IL4 may provide protection against deleterious effects of PGN stimulation by maintaining a balanced microglial cell response and the survival.