Mycoplasma triggering of nitric oxide production by central nervous system glial cells and its inhibition by glucocorticoids.
The same cytokines that have been implicated in the pathology of central nervous system (CNS) inflammatory diseases and demyelinating diseases are also associated with the induction of nitric oxide (NO) production by macrophages and other somatic cells. Recently we have showed that mycoplasma can trigger the production of tumor necrosis factor (TNF)alpha and eicosanoids in rat astrocytes. In the present study, the effect of mycoplasma on NO production in rat glial cells was assessed. The addition of 10 micrograms/ml of membranes derived from M. capricolum (sheep isolate), M. fermentans (human isolate), or lipopolysaccharide (LPS) led to a 15- to 20-fold increase in NO production. The glucocorticoids dexamethasone and corticosterone, but not progesterone, markedly inhibited NO production. The addition of glucocorticoid prior or conjointly with the activator prevented large amounts of NO from being formed. Even when glucocorticoids were added 5 or 24 h after activation, effective inhibition of NO production was obtained. Thus, it is likely that glucocorticoids exert some of their ameliorating effects in neurological diseases by reducing the production of NO, cytokines and prostaglandins in the CNS.
Department of Neurology, Hadassah University Hospital, Jerusalem, Israel.
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T
Brenner
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A
Yamin
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Gallily
D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis; D005938:Glucocorticoids / Q000494:pharmacology*; D009174:Mycoplasma / Q000502:physiology*; D016858:Mycoplasma fermentans / Q000502:physiology*; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D005938:Glucocorticoids; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D003907:Dexamethasone; D015232:Dinoprostone