Protein kinase A mediates microglial activation induced by plasminogen and gangliosides.
- Author:
Kyoung Jin MIN
1
;
Myung Soon YANG
;
Ilo JOU
;
Eun hye JOE
Author Information
1. Department of Pharmacology, Ajou University School of Medicine, Suwon 442-721, Korea. ehjoe@madang.ajou.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
brain inflammation;
cAMP response element binding protein (CREB);
gangliosides;
microglia;
plasminogen;
protein kinase A
- MeSH:
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
- From:Experimental & Molecular Medicine
2004;36(5):461-467
- CountryRepublic of Korea
- Language:English
-
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.
