DOES IL-33 POTENTIATE OR DEPRESSAMPA RECEPTOR RESPONSE?

The present study aimed at understanding the effect of inteleukin-33 (IL-33), a proinflammatory cytokine, on α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) receptor responses. IL-33 potentiated whole-cell membrane currents through AMPA receptor channels consisting of the GluA1 subunit expressed in Xenopus oocytes. In contrast, the amplitude of AMPA receptor-mediated miniature excitatory postsynaptic currents (AMPA-mEPSCs), which were monitored from the CA1 region of hippocampal slices of IL-33-deficient mice, was significantly increased as compared with the amplitude for wild-type control mice, without affecting the rate of AMPA-mEPSCs. There was no significant difference in the cell surface localization of the AMPA receptor subunits GluA1 and GluA2 in the hippocampus between IL-33-deficient mice and wild-type control mice. The results of the present study suggest that IL-33 has the potential to potentiate AMPA receptor responses and that in the IL-33-deficient mouse brain, expression of IL-33 might be upregulated as a compensative reaction of chronic IL-33 loss, causing an enhancement in the AMPA receptor responses, regardless of cell surface localization of the GluA1 and GluA2 subunits.