Prostaglandin modulates TLR3-induced cytokine expression in human astroglioma cells

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 E-2 (PGE(2)) 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-kappa B and extracellular stress-related kinase 1/2 (ERK1/2), which significantly decreased following PGE(2) treatment. In addition, PGE(2) increased the phosphorylation and inactivation of glycogen synthesis kinase-3 beta (GSK-3 beta), whereas poly(I:C) decreased it. We observed that PGE(2) decreased tumor necrosis factor-alpha (TNF-alpha) production evoked by poly(I:C), whereas PGE(2) 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-kappa B, ERK1/2 and GSK-3 beta signaling pathways. (C) 2014 Elsevier B.V. All rights reserved.