کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4325799 1614039 2011 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Neurotoxic factors released by stimulated human monocytes and THP-1 cells
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Neurotoxic factors released by stimulated human monocytes and THP-1 cells
چکیده انگلیسی

Activated monocytes/macrophages are known to release toxic materials. Identification of these materials is important for developing more effective treatments for inflammatory disorders where self attack occurs. We stimulated human monocytes and THP-1 cells with LPS/IFNγ and measured the toxic effects of their conditioned media against differentiated human NT-2 cells. Their cytotoxicity, as measured by LDH release, was reduced by half when their conditioned media was passed through a 3 kDa cutoff filter, indicating an equal division between high and low molecular weight materials. When the high molecular weight components tumor necrosis factor-α (TNFα), interleukin-1β (IL-1β), and IL-6 were removed from the conditioned medium by specific antibodies, the toxicity was reduced by 37–38%. When prostaglandin production was blocked by treatment with the COX inhibitors acetylsalicylic acid and ibuprofen, toxicity was reduced by 15–16%. When oxygen free radical production was blocked by the NADPH inhibitor diphenylene iodonium (DPI) the toxicity was reduced by 17–18%. Treatment with the nitric oxide scavenger carboxy-phenyl-tetramethylimidazolineoxyl-oxide, or the NOS inhibitor NG-monomethylene-l-arginine, attenuated the toxicity by about 20%. Removal of released glutamate by glutamate decarboxylase also attenuated the toxicity by 12–13%. In combination, these treatments reduced the toxicity by approximately 50% accounting for the low molecular weight component toxicity. About 10% of the overall toxicity, which was associated with the high molecular weight component, was not identified. Optimal antiinflammatory therapy may require combined suppression of these identified toxin-generating pathways as well as relatively minor pathways yet to be identified.


► Activated monocytes and microglia are known to release neurotoxic materials.
► Removal of TNFα, IL-1β, and IL-6 reduced toxicity to NT-2 cells by 38–40%.
► Small molecules, free radicals and prostaglandins, constitute 50% of total toxicity.
► Optimal therapy may require combined suppression of these pathways.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain Research - Volume 1400, 11 July 2011, Pages 99–111
نویسندگان
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