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 cytok ine, interleukin-1 (IL-1), the receptor and post-receptor mechanisms that m ediate IL-1 effects in this cell type are complex and need further investig ation. 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 recept or/IL-1 receptor accessory protein complex, as demonstrated by the ability of blocking monoclonal antibodies against these receptors to attenuate NF k appaB activation. In addition to NF kappaB activation, IL-1 beta is also ab le to phosphorylate Akt, as demonstrated by Western blot. The observation t hat addition of wortmanin, that specifically blocks Akt phosphorylation, al so attenuates NF kappaB activation can be interpreted that Akt phosphorylat ion 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 ac tivation also attenuate IL-1 beta -induced Akt phosphorylation, despite the fact that IL-4 and IL-10 in isolation induced Akt phosphorylation, All the se findings point to an interaction between Akt and NF kappaB-dependent IL- 1 signaling in the primary culture of astrocytes.