Inhibition of microglial nitric oxide production by hydrocortisone and glucocorticoid precursors.
Viral and bacterial infection in the central nervous system can induce nitric oxide production, which serves as a major host defense against invading microorganisms. Glucocorticoids secretion is enhanced and immune responses are diminished in stressed animals or in patients suffering depression. Using N9 microglial cells, this study tested the hypothesis that glucocorticoids and their precursors caused an impaired immune defense in animals because these compounds could inhibit microglial nitric oxide production. Results indicated that both hydrocortisone and the synthetic glucocorticoid, dexamethasone, were potent inhibitors of the microglial nitric oxide production. While glucocorticoid precursors were not as potent as hydrocortisone, the potency of these precursors increased linearly as they advanced on the biosynthesis pathway. Northern and Western blot analyses indicated that hydrocortisone and dexamethasone might interfere with the inducible nitric oxide synthase at either the transcription or at the post-translational level, depending on the concentrations used. These results suggest that glucocorticoids have the ability to block nitric oxide production by microgila, which could partially explain the impaired immune protection against infection in the central nervous system in stressed animals.
Chang
J Y
JY
Department of Anatomy, University of Arkansas for Medical Sciences, Little Rock 72205, USA. changjasony@exchange.uams.edu
Liu
L Z
LZ
D000818:Animals; D002460:Cell Line; D003907:Dexamethasone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006854:Hydrocortisone / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015735:Mifepristone / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D009569:Nitric Oxide; D015735:Mifepristone; D003907:Dexamethasone; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D006854:Hydrocortisone