Abstract
Prostaglandins (PGs) and nitric oxide (NO) play major roles in regulating inflammation, immune functions, blood vessel dilatation and neurotransmission. NO is formed from the terminal guanidino nitrogen atom of L-arginine by the enzyme NO synthase (NOS). The constitutive isoform of NOS is present in endothelial and neuronal cells, whereas the inducible isoform (iNOS) is expressed in macrophages and other cell types after stimulation with cytokines and proinflammatory agents such as lipopolysaccharide (LPS). PGs are generated by metabolic conversion of arachidonic acid (AA) to PGs by the enzyme cyclooxygenase (COX). Also COX has been found in two isoforms, the constitutive enzyme (COX-1) which is expressed in almost every tissue and releases low levels of PGs involved in physiological functions, and the inducible isoform (COX-2), which is the major isoform expressed in inflammatory cells and can synthesize large amounts of PGs in response to inflammatory stimuli. The cross talk between these two pathways is of particular interest at inflammatory sites as the synthesis of prostanoids and NO is often elicited by the same stimuli. Microglial cells, the brain resident macrophages, express both iNOS and COX-2 and produce large amounts of both NO and PGs in response to LPS1,2. In a previous study we have shown that NO downregulates microglial COX-2 expression and PG production2, yet in other systems, including the widely used monocytic/macrophagic cell line RAW 264.7, NO was reported to stimulate PG synthesis3.
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Guastadisegni, C., Minghetti, L., Nicolini, A., Polazzi, E., Balduzzi, M., Levi, G. (1999). Different Effects of Reactive Nitrogen Intermediates on Prostaglandin E2 Synthesis in Cultured Rat Microglia and Raw 264.7 Cells. In: Honn, K.V., Marnett, L.J., Nigam, S., Dennis, E.A. (eds) Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury, 4. Advances in Experimental Medicine and Biology, vol 469. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4793-8_26
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DOI: https://doi.org/10.1007/978-1-4615-4793-8_26
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