Linomide-mediated protection of oligodendrocytes is associated with inhibition of nitric oxide production and IL-1beta expression in Lewis rat glial cells.
Linomide is a synthetic immunomodulator that down-regulates autoimmune response without inducing systemic immunosuppression. Linomide effectively inhibits severe experimental autoimmune diseases, like experimental allergic encephalomyelitis (EAE), a model of multiple sclerosis (MS). Here we report that Linomide suppresses nitric oxide (NO) production by microglia and astrocytes derived from newborn rats and prevented oligodendrocyte damage. Linomide strongly inhibited interleukin (IL) 1 betamRNA expression on glial cells, suggesting a potential mechanism for inhibition of NO production by Linomide. These results demonstrate that Linomide-mediated inhibition of NO production by glial cells could explain the preventive and therapeutic effects of Linomide in EAE and perhaps also MS. However, Linomide at higher dose [correction of doss] (10(-5) M) resulted in direct oligodendrocyte damage.
Xiao
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Division of Neurology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
Bail
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XF
Zhang
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Hedlund
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Link
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D000276:Adjuvants, Immunologic / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000831:Animals, Newborn; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006912:Hydroxyquinolines / Q000494:pharmacology* / Q000633:toxicity; D007375:Interleukin-1 / Q000096:biosynthesis*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011917:Rats, Inbred Lew
D000276:Adjuvants, Immunologic; D006912:Hydroxyquinolines; D007375:Interleukin-1; D012333:RNA, Messenger; D009569:Nitric Oxide; C045282:roquinimex; D007770:L-Lactate Dehydrogenase