Interleukin-1 signaling in mouse astrocytes involves Akt: a study with interleukin-4 and interleukin-10

Although astrocytes are well known to respond to the pro-inflammatory cytokine, interleukin-1 (IL-1), the receptor and post-receptor mechanisms that mediate IL-1 effects in this cell type are complex and need further investigation. Using electrophoretic mobility shift assay (EMSA), we show that IL-1 beta -induced NF kappaB activation in primary culture of mouse astrocytes is mediated by the interaction of this cytokine with the IL-1 type I receptor/IL-1 receptor accessory protein complex, as demonstrated by the ability of blocking monoclonal antibodies against these receptors to attenuate NF kappaB activation. In addition to NF kappaB activation, IL-1 beta is also able to phosphorylate Akt, as demonstrated by Western blot. The observation that addition of wortmanin, that specifically blocks Akt phosphorylation, also attenuates NF kappaB activation can be interpreted that Akt phosphorylation interacts with IL-1 signaling pathways. Furthermore, anti-inflammatory cytokines such as IL-4 and IL-10 that block IL-1 beta -induced NF kappaB activation also attenuate IL-1 beta -induced Akt phosphorylation, despite the fact that IL-4 and IL-10 in isolation induced Akt phosphorylation, All these findings point to an interaction between Akt and NF kappaB-dependent IL-1 signaling in the primary culture of astrocytes.