title: 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.affiliation: Department of Physiology and Dental Research Institute, Seoul National University School of Dentistry, Seoul 110-749, Republic of Korea.
authors.forename: Keimin
authors.initials: K
authors.lastname: Lee
authors.affiliation: Department of Physiology and Dental Research Institute, Seoul National University School of Dentistry, Seoul 110-749, Republic of Korea.
authors.forename: Soo-Jeong
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Physiology and Dental Research Institute, Seoul National University School of Dentistry, Seoul 110-749, Republic of Korea.
authors.forename: Donghoon
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Physiology, Kangwon National University School of Medicine, Chuncheon 200-701, Republic of Korea.
authors.forename: Su-Hyun
authors.initials: SH
authors.lastname: Jo
authors.affiliation: Department of Physiology and Dental Research Institute, Seoul National University School of Dentistry, Seoul 110-749, Republic of Korea.
authors.forename: Sung
authors.initials: S
authors.lastname: Joong Lee
authors.affiliation: Department of Physiology and Dental Research Institute, Seoul National University School of Dentistry, Seoul 110-749, Republic of Korea. Electronic address: sychoi@snu.ac.kr.
authors.forename: Se-Young
authors.initials: SY
authors.lastname: Choi
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001254:Astrocytoma / Q000378:metabolism*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002540:Cerebral Cortex / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000502:physiology; D011453:Prostaglandins / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D051196:Toll-Like Receptor 3 / Q000819:agonists / Q000378:metabolism*
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D011453:Prostaglandins; C495344:TLR3 protein, human; C530472:TLR3 protein, rat; D051196:Toll-Like Receptor 3; D000242:Cyclic AMP; D000071679:Glycogen Synthase Kinase 3 beta; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Astrocyte; Cytokine; G-protein coupled receptor; Prostaglandin; Toll-like receptor