Up-regulation of cyclooxygenase-2 expression in cultured microglia by prostaglandin E2, cyclic AMP and non-steroidal anti-inflammatory drugs

The European Journal of Neuroscience
L MinghettiG Levi

Abstract

Cyclooxygenase-2, the inducible isoform of cyclooxygenase, is highly expressed in microglial cells activated by bacterial lipopolysaccharide and is a major regulatory factor in the synthesis of prostanoids, such as prostaglandins, prostacyclin and thromboxanes. Since prostanoids are potent modulators of inflammation, immune responses and neurotoxicity, the regulation of their synthesis may be crucial for balancing microglial neuroprotective and neurotoxic activities. The present study shows that expression of cyclooxygenase-2 and prostanoid production in cultured rat microglia activated by lipopolysaccharide is up-regulated by cyclic AMP (cAMP), as indicated by experiments performed in the presence of adenylyl cyclase activators, cAMP analogues and protein kinase A-specific inhibitors. Exogenous prostaglandin E2 (PGE2), which elevates the cAMP level in microglial cells, also increased the lipopolysaccharide-induced expression of cyclooxygenase-2 and production of thromboxane in a dose- and time-dependent manner. The observations that the lipopolysaccharide-induced prostanoid production was specifically increased by 11-deoxy-16,16-dm PGE2, a selective agonist at the PGE2 receptor EP2 coupled to the activation of adenylyl cyclase...Continue Reading

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