Differential roles of PKA and Epac on the production of cytokines in the endotoxin-stimulated primary cultured microglia.

Journal of Molecular Neuroscience : MN
Jian LiuBuwei Yu

Abstract

To further understand the anti-inflammatory effect of adenosine cyclic 3',5'-monophosphate (cAMP), we examined the effect of protein kinase A (PKA) and cAMP-responsive guanine nucleotide exchange factor (Epac) on the transcription and production of cytokines and on the activity of mitogen-activated protein kinases (MAPK) p38 and glycogen synthase kinase-3β (GSK-3β) in endotoxin-treated rat primary cultured microglia. The PKA specific agonist N6-benzoyladenosine-3,5-cAMP (6-Bnz-cAMP) not only inhibited the transcription and production of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) but also enhanced the transcription and expression of IL-10, while the Epac selective analog 8-(4-chlorophenylthio)-2-O-methyladenosine-3,5-cAMP (8-pCPT-2'-O-Me-cAMP) merely repressed the TNF-α expression. Western blots assays indicated that 6-Bnz-cAMP significantly inhibited lipopolysaccharide-induced activation of both p38 and GSK-3β in a dose-dependent manner; in contrast, 8-pCPT-2'-O-Me-cAMP only slightly repressed GSK-3β activity at large doses. Pretreatment with H-89, a specific PKA antagonist, could completely reverse the effect of 6-Bnz-cAMP on cytokines expressions and kinases activities but had no effect on the performance of 8...Continue Reading

References

May 21, 1999·Multiple Sclerosis : Clinical and Laboratory Research·M YoshikawaM Sawada
Oct 12, 2001·Glia·F Aloisi
Oct 29, 2002·Nature Cell Biology·Jorrit M EnserinkJohannes L Bos
Sep 25, 2003·Nature Reviews. Molecular Cell Biology·Johannes L Bos
Jun 15, 2004·Neuroreport·Heasuk Lee, Kyoungho Suk
Oct 23, 2004·The Journal of Biological Chemistry·Huie JingDoina Ganea
Jan 7, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·David M AronoffMarc Peters-Golden
May 10, 2005·Science·Greg Miller
Feb 2, 2006·Molecular and Cellular Biology·Jiyan ZhangAnning Lin
Nov 28, 2007·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Gwenn A Garden, Thomas Möller

❮ Previous
Next ❯

Citations

Nov 29, 2013·Drug Design, Development and Therapy·Annette J TheronRonald Anderson
Feb 14, 2013·The Journal of Biological Chemistry·Yi QuanRay Dingledine
Jul 3, 2013·Journal of Neurochemistry·Junghyung ParkDong-Seok Lee
Aug 8, 2018·The Journal of Physiological Sciences : JPS·Yuko KatoYoshihiro Ishikawa
Nov 25, 2016·Journal of Neuroinflammation·Diogo Lobo-SilvaMargarida Saraiva

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.