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Abstract:
Release of nitric oxide and TNF-alpha, a toxic cytokine, have been reported to accelerate neuronal damage under several pathological conditions, such as trauma or ischemia in the central nervous system. In the present study, we tested the effect of alprostadil alfadex, a prostaglandin E I analog, on cultured microglia from the rat spinal cord. The cultured microglia were exposed to lipopolysaccharide (LPS) (100 ng/ml), an endotoxin, for 24 h, then the released nitric oxide and TNF- alpha in the culture media was analyzed. The released nitric oxide was detected by the Griess reaction and released TNF- alpha was measured using ELISA method. The LPS-induced nitric oxide release was inhibited by the simultaneous addition of alprostadil alfadex in a dose-dependent manner (0.1-100 muM). The LPS-induced TNF-alpha release was also inhibited by alprostadil alfadex addition (0.1-100 muM). The IC50 values of alprostadil alfadex on nitric oxide and TNF-alpha release were about 1 and 10 muM, respectively. These results suggest that prostaglandin El possibly protects spinal cord neurons from several types of neurodegenerative damage, not only via increased blood supply, but also via inhibition of pathological immunoreactions of activated microglia. (C) 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
