The Interplay between Cyclic AMP, MAPK, and NF-κB Pathways in Response to Proinflammatory Signals in Microglia.
Cyclic AMP is an important intracellular regulator of microglial cell homeostasis and its negative perturbation through proinflammatory signaling results in microglial cell activation. Though cytokines, TNF-α and IL-1β, decrease intracellular cyclic AMP, the mechanism by which this occurs is poorly...
| Publicado en: | BioMed Research International Vol. 2015; pp. 1 - 19 |
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| Autores principales: | , , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
2/5/2015
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=109273341&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 109273341 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 23146133 FT2T jtl: BioMed Research International issn: 23146133 maglogo: N pubinfo: dt: 2/5/2015 vid: 2015 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 109273341 109273341 109273341 10.1155/2015/308461 109273341 ppf: 1 ppct: 18 formats: fmt: @attributes: type: P tig: atl: The Interplay between Cyclic AMP, MAPK, and NF-κB Pathways in Response to Proinflammatory Signals in Microglia. aug: au: Ghosh, Mousumi Aguirre, Vladimir Wai, Khine Felfly, Hady Dietrich, W. Dalton Pearse, Damien D. affil: The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL 33136, USA sug: subj: Inflammation Cyclic AMP NF-kappa B Protein Kinases Human Funding Source Immunohistochemistry Analysis of Variance Post Hoc Analysis Confidence Intervals Data Analysis Software Academic Medical Centers Florida Blotting, Western ab: Cyclic AMP is an important intracellular regulator of microglial cell homeostasis and its negative perturbation through proinflammatory signaling results in microglial cell activation. Though cytokines, TNF-α and IL-1β, decrease intracellular cyclic AMP, the mechanism by which this occurs is poorly understood. The current study examined which signaling pathways are responsible for decreasing cyclic AMP in microglia following TNF-α stimulation and sought to identify the role cyclic AMP plays in regulating these pathways. In EOC2 microglia, TNF-α produced a dramatic reduction in cyclic AMP and increased cyclic AMP-dependent PDE activity that could be antagonized by Rolipram, myristoylated-PKI, PD98059, or JSH-23, implicating a role for PDE4, PKA, MEK, and NF-κB in this regulation. Following TNF-α there were significant increases in iNOS and COX-2 immunoreactivity, phosphorylated ERK1/2 and NF-κB-p65, IκB degradation, and NF-κB p65 nuclear translocation, which were reduced in the presence of high levels of cyclic AMP, indicating that reductions in cyclic AMP during cytokine stimulation are important for removing its inhibitory action on NF-κB activation and subsequent proinflammatory gene expression. Further elucidation of the signaling crosstalk involved in decreasing cyclic AMP in response to inflammatory signals may provide novel therapeutic targets for modulating microglial cell activation during neurological injury and disease. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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