Induction of COX-2 enzyme and down-regulation of COX-1 expression by lipopolysaccharide (LPS) control prostaglandin E2 production in astrocytes.

摘要: Pathological conditions and pro-inflammatory stimuli in the brain induce cyclooxygenase-2 (COX-2), a key enzyme arachidonic acid metabolism mediating production of prostanoids that, among other actions, have strong vasoactive properties. Although low basal cerebral COX-2 expression has been reported, is strongly induced by challenges, whereas COX-1 constitutively expressed. However, contribution these enzymes prostanoid formation varies depending on cell type. Astrocyte feet surround microvessels release molecules that can trigger vascular responses. Here, we investigate regulation induction its role generation after challenge with bacterial lipopolysaccharide (LPS) astroglia. Intracerebral administration LPS rodents mainly astroglia microglia, was predominant microglia did not increase. In cultured astrocytes, microsomal prostaglandin-E2 (PGE2) synthase-1, mediated MyD88-dependent NFκB pathway influenced mitogen-activated protein kinase pathways. Studies COX-deficient cells using COX inhibitors demonstrated high PGE2 and, to lesser extent, LPS. contrast, down-regulated an fashion, deficiency increased The results show astrocytes respond COX-2-dependent prostanoids, PGE2, suggest coordinated down-regulation facilitates TLR-4 activation. These effects might blood flow responses inflammation.