Prostaglandin modulates TLR3-induced cytokine expression in human astroglioma cells.

Abstract

Cyclooxygenase (COX) products and pattern recognition receptors are important modulators of neuroinflammation; however, the role of prostaglandins and toll-like receptor (TLR) signaling and the functional crosstalk between COX modulators remains unclear, especially in astrocytes that closely modulate neuronal functions. Here, we studied the effect of prostaglandins on toll-like receptor 3 (TLR3)-induced cytokine expression in human astroglioma CRT-MG cells. Prostaglandin E2 (PGE2) was shown to increase cytosolic cAMP levels in an EP2 receptor dependent manner. Interestingly, the TLR3 agonist polyinosinic:polycytidylic acid (poly(I:C)) mediated phosphorylation of NF-κB and extracellular stress-related kinase 1/2 (ERK1/2), which significantly decreased following PGE2 treatment. In addition, PGE2 increased the phosphorylation and inactivation of glycogen synthesis kinase-3β (GSK-3β), whereas poly(I:C) decreased it. We observed that PGE2 decreased tumor necrosis factor-α (TNF-α) production evoked by poly(I:C), whereas PGE2 potentiated poly(I:C)-triggered interleukin-8 (IL-8) production. These results suggest that prostaglandin modulates the TLR3-mediated cytokine profile in astrocytes via EP2 receptors and regulates the NF-κB, ERK1/2 and GSK-3β signaling pathways.

• Authors: Keimin Lee, Soo-Jeong Kim, Donghoon Kim, Su-Hyun Jo, Sung Joong Lee, Se-Young Choi
• Journal: Brain research (Brain Res) Vol. 1589 Pg. 54-60 (11 17 2014) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 25014275 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Cytokines
• NF-kappa B
• Prostaglandins
• TLR3 protein, human
• TLR3 protein, rat
• Toll-Like Receptor 3
• Cyclic AMP
• Glycogen Synthase Kinase 3 beta
• Extracellular Signal-Regulated MAP Kinases

Topics

• Animals
• Astrocytes (metabolism)
• Astrocytoma (metabolism)
• Blotting, Western
• Cell Line, Tumor
• Cerebral Cortex (metabolism)
• Cyclic AMP (metabolism)
• Cytokines (metabolism)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Glycogen Synthase Kinase 3 beta (metabolism)
• Humans
• NF-kappa B (metabolism)
• Phosphorylation (physiology)
• Prostaglandins (metabolism)
• Rats, Sprague-Dawley
• Real-Time Polymerase Chain Reaction
• Toll-Like Receptor 3 (agonists, metabolism)