Exp Mol Med.  2004 Oct;36(5):461-467.

Protein kinase A mediates microglial activation induced by plasminogen and gangliosides

• Min KJ
• Yang MS
• Jou I
• Joe EH

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.

Keyword

brain inflammation; cAMP response element binding protein (CREB); gangliosides; microglia; plasminogen; protein kinase A

MeSH Terms

Animals
Carbazoles/pharmacology
Cell Line
Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors/*physiology
DNA-Binding Protein, Cyclic AMP-Responsive/metabolism
DNA-Binding Proteins/metabolism
Gangliosides/pharmacology/*physiology
Gene Expression Regulation
Indoles/pharmacology
Interleukin-1/genetics
Isoquinolines/pharmacology
Mice
Microglia/drug effects/*enzymology/*immunology
NF-kappa B/metabolism
Nitric-Oxide Synthase/genetics
Plasminogen/pharmacology/*physiology
Pyrroles/pharmacology
RNA, Messenger/analysis/metabolism
Rats
Research Support, Non-U.S. Gov't
Sulfonamides/pharmacology
Tumor Necrosis Factor-alpha/genetics