The Interplay between Cyclic AMP, MAPK, and NF-κB Pathways in Response to Proinflammatory Signals in Microglia
Joint Authors
Ghosh, Mousumi
Aguirre, Vladimir
Wai, Khine
Felfly, Hady
Dietrich, W. Dalton
Pearse, Damien D.
Source
Issue
Vol. 2015, Issue 2015 (31 Dec. 2015), pp.1-18, 18 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2015-02-05
Country of Publication
Egypt
No. of Pages
18
Main Subjects
Abstract EN
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.
American Psychological Association (APA)
Ghosh, Mousumi& Aguirre, Vladimir& Wai, Khine& Felfly, Hady& Dietrich, W. Dalton& Pearse, Damien D.. 2015. The Interplay between Cyclic AMP, MAPK, and NF-κB Pathways in Response to Proinflammatory Signals in Microglia. BioMed Research International،Vol. 2015, no. 2015, pp.1-18.
https://search.emarefa.net/detail/BIM-1054989
Modern Language Association (MLA)
Ghosh, Mousumi…[et al.]. The Interplay between Cyclic AMP, MAPK, and NF-κB Pathways in Response to Proinflammatory Signals in Microglia. BioMed Research International No. 2015 (2015), pp.1-18.
https://search.emarefa.net/detail/BIM-1054989
American Medical Association (AMA)
Ghosh, Mousumi& Aguirre, Vladimir& Wai, Khine& Felfly, Hady& Dietrich, W. Dalton& Pearse, Damien D.. The Interplay between Cyclic AMP, MAPK, and NF-κB Pathways in Response to Proinflammatory Signals in Microglia. BioMed Research International. 2015. Vol. 2015, no. 2015, pp.1-18.
https://search.emarefa.net/detail/BIM-1054989
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1054989