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Protein kinase A mediates microglial activation induced by plasminogen and gangliosides.

Authors
Min, KJ; Yang, MS; Jou, I; Joe, EH
Citation
Experimental & molecular medicine, 36(5):461-467, 2004
Journal Title
Experimental & molecular medicine
ISSN
1226-36132092-6413
Abstract
In the injured brain, microglia is known to be activated and produce proinflammatory mediators such as interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and inducible nitric oxide synthase (iNOS). We investigated the role of protein kinase A (PKA) in microglial activation by both plasminogen and gangliosides in rat primary microglia and in the BV2 immortalized murine microglial cell line. Both plasminogen and gangliosides induced IL-1beta, TNF-alpha and iNOS mRNA expression, and that this expression was inhibited by the addition of the PKA inhibitors, KT5720 and H89. Both plasminogen and gangliosides activated PKA and increased the DNA binding activity of the cAMP response element- binding protein (CREB). Furthermore, KT5720 and H89 reduced the DNA binding activities of CREB and NF-kappaB in plasminogen-treated cells. These results suggest that PKA plays an important role in plasminogen and gangliosides- induced microglial activation.
MeSH terms
AnimalsCarbazoles/pharmacologyCell LineCyclic AMP Response Element-Binding Protein/metabolismCyclic AMP-Dependent Protein Kinase Type IICyclic AMP-Dependent Protein Kinases/antagonists & inhibitors/*physiologyDNA-Binding Proteins/metabolismGangliosides/pharmacology/*physiologyGene Expression RegulationIndoles/pharmacologyInterleukin-1/geneticsIsoquinolines/pharmacologyMiceMicroglia/drug effects/*enzymology/*immunologyNF-kappa B/metabolismNitric Oxide Synthase/geneticsNitric Oxide Synthase Type IIPlasminogen/pharmacology/*physiologyPyrroles/pharmacologyRNA, Messenger/analysis/metabolismRatsSulfonamides/pharmacologyTumor Necrosis Factor-alpha/genetics
DOI
10.1038/emm.2004.58
PMID
15557818
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
AJOU Authors
양, 명순주, 일로조, 은혜
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