Interleukin‐1 beta‐induced expression of the prostaglandin E₂‐receptor subtype EP3 in U373 astrocytoma cells depends on protein kinase C and nuclear factor‐kappaB

Abstract

Both interleukin-1b (IL-1b) and prostaglandins (PGs) are important mediators of physiological and pathophysiological processes in the brain. PGE 2 exerts its effects by binding to four different types of PGE 2 receptors named EP1-EP4. EP3 has found to be expressed in neurons, whereas expression of EP3 in glial cells has not been reported in the brain yet. Here we describe IL-1b-induced EP3 receptor expression in human astrocytoma cells, primary astrocytes of rat and human origin and in rat brain. Using western blot, we found a marked up-regulation of EP3 receptor synthesis in human and rat primary glial cells. Intracerebroventricular administration of IL-1b stimulated EP3 receptor synthesis in rat hippocampus.The analysis of involved signal transduction pathways by pathway-specific inhibitors revealed an essential role of protein kinase C and nuclear factor-jB in astrocytic IL-1b-induced EP3 synthesis. Our data suggest that PGE 2 signaling in the brain may be altered after IL-1b release due to up-regulation of EP3 receptors. This might play an important role in acute and chronic conditions such as cerebral ischemia, traumatic brain injury, HIV-encephalitis, Alzheimer's disease and prion diseases in which a marked up-regulation of IL-1b is followed by a prolonged increase of PGE 2 levels in the brain.

The CCAAT/enhancer-binding protein delta/miR135a/thrombospondin 1 axis mediates PGE2-induced angiogenesis in Alzheimer's disease

“…1A). Four PGE2 receptors have been identified in astrocytes (Fiebich et al, 2001;Waschbisch et al, 2006). To assess which receptor plays a potent role in the PGE2-induced CEBPD activation in astrocytes, four selective agonists of each EP subtype [ONO-DI-004 (DI-004) for EP1, ONO-AE1-259 (AE1-259) for EP2, ONO-AE-248 (AE-248) for EP3 and ONO-AE1-329 (AE1-329) for EP4] were used to treat U373MG cells.…”

Intercellular Signaling Pathway among Endothelia, Astrocytes and Neurons in Excitatory Neuronal Damage

“…These results indicate that the EP3 receptor is locally induced by KA in hippocampal astrocytes, which may receive PGE 2 from endothelial cells. Preceding publications have already shown that EP3 mRNA is expressed in cultured astrocytes [34], and EP3 protein is induced in astrocytomas by interleukin-1β [35]. These findings indicate that astrocytic EP3 receptors may be upregulated under pathological conditions, and endothelial PGE 2 may directly activate EP3 receptors on astrocytic end-feet, not distant neuronal EP receptors in neurotoxic brain diseases, such as epileptic seizures.…”

Acute effects of prostaglandin E1 and E2 on vascular reactivity and blood flow in situ in the chick chorioallantoic membrane

“…The size of the EP 3 receptor has been reported as low as 33-38 kD in splice variants [28,29] while the full length protein determined by amino acid comparison is estimated at ~55-63 kD. There are two sites of possible N-linked glycosylation, which can yield products of 65-75 kD that have been previously detected on Western blots [28,29]. Together these results suggest that constrictive effects of PGE 1 and PGE 2 are mediated at least in part by EP 3 receptors.…”

“…EP 2 & 4 receptor subtypes have been shown to exist in chicken by molecular cloning [35], and our data support the existence of EP 3 receptors in the developing CAM (Fig 12). EP 3 receptors mediate contraction of the uterus, inhibition of gastric acid secretion, modulation of neurotransmitters, lipolysis, sodium and water reabsorption in kidney tubules and secretion of catecholamines [4,25,29,36-38]. The vasoactive effects of PGEs on pulmonary arteries appear to depend upon a variety of factors including the state of activation of the vascular smooth muscle prior to exposure to the lipid, whether the vessels are arteries or veins and/or the subtype of EP receptor expressed.…”