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.
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