Protein kinase A mediates microglial activation induced by plasminogen and gangliosides

In the injured brain, microglia is known to be activated and produce proinflamatory media-tors such as interleukin-1β (IL-1β), tumor necro-sis factor-α (TNF-α) and inducible nitric oxide protein kinase A (PKA) in microglial activation by both plasminogen and gangliosides in rat primary microglia and in the BV2 imortalized murine microglial cell line. Both plasminogen and gangliosides induced IL-1β, TNF-α and iNOS mRNA expression, and that this expression was inhibited by the addition of the PKA inhibitors, KT5720 and H89. Both plasminogen and gan-gliosides activated PKA and increased the DNA binding activity of the cAMP response element- binding protein (CREB). Furthermore, KT5720 CREB and NF-κB in plasminogen-treated cells. These results sugest that PKA plays an im-portant role in plasminogen and gangliosides- induced microglial activation. KCI Citation Count: 17