title: Protein kinase A mediates microglial activation induced by plasminogen and gangliosides.
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.
authors.affiliation: Department of Pharmacology, Ajou University, School of Medicine, Suwon 442-721, Korea.
authors.forename: Kyoung-Jin
authors.initials: KJ
authors.lastname: Min
authors.forename: Myung-Soon
authors.initials: MS
authors.lastname: Yang
authors.forename: Ilo
authors.initials: I
authors.lastname: Jou
authors.forename: Eun-hye
authors.initials: EH
authors.lastname: Joe
mesh_terms: D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005732:Gangliosides / Q000494:pharmacology / Q000502:physiology*; D005786:Gene Expression Regulation; D007211:Indoles / Q000494:pharmacology; D007375:Interleukin-1 / Q000235:genetics; D007546:Isoquinolines / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology*; D016328:NF-kappa B / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D010958:Plasminogen / Q000494:pharmacology / Q000502:physiology*; D011758:Pyrroles / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D013449:Sulfonamides / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D002227:Carbazoles; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D005732:Gangliosides; D007211:Indoles; D007375:Interleukin-1; D007546:Isoquinolines; D016328:NF-kappa B; D011758:Pyrroles; D012333:RNA, Messenger; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; C057416:KT 5720; D010958:Plasminogen; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C496318:Nos2 protein, rat; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide