Abstract | BACKGROUND: METHODS: Primary microglial and astrocytic cell cultures were prepared from cerebral cortices of neonatal rats. The control cells were treated with LPS, an accepted inducer of pro-inflammatory properties in glial cells, and the experimental groups with LPS and DMF in different concentrations. After stimulation/incubation, the generation of nitric oxide (NO) in the cell culture supernatants was determined by measuring nitrite accumulation in the medium using Griess reagent. After 6 hours of treatment RT-PCR was used to determine transcription levels of iNOS, IL-1beta, IL-6 and TNF-alpha mRNA in microglial and astrocytic cell cultures initially treated with DMF, followed after 30 min by LPS treatment. Moreover, we investigated possible involvement of the ERK and Nrf-2 transduction pathway in microglia using western blot analysis. RESULTS: Pretreatment with DMF decreased synthesis of the proinflammatory mediators iNOS, TNF-alpha, IL-1beta and IL-6 at the RNA level in activated microglia and astrocytes in vitro, associated with a decrease in ERK phosphorylation in microglia. CONCLUSIONS: Collectively, these results suggest that the neuroprotective effects of DMF may be in part functionally attributable to the compound's ability to inhibit expression of multiple neuroinflammatory mediators in brain of MS patients.
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Authors | Henrik Wilms, Jobst Sievers, Uta Rickert, Martin Rostami-Yazdi, Ulrich Mrowietz, Ralph Lucius |
Journal | Journal of neuroinflammation
(J Neuroinflammation)
Vol. 7
Pg. 30
(May 19 2010)
ISSN: 1742-2094 [Electronic] England |
PMID | 20482831
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Inflammatory Agents, Non-Steroidal
- Dimethyl Fumarate
- Extracellular Signal-Regulated MAP Kinases
- Fumarates
- Interleukin-1beta
- Interleukin-6
- Nitric Oxide
- Nitric Oxide Synthase Type II
- Nitrites
- RNA, Messenger
- Tumor Necrosis Factor-alpha
- NF-E2-Related Factor 2
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Topics |
- Animals
- Rats
- Anti-Inflammatory Agents, Non-Steroidal
(pharmacology)
- Astrocytes
(drug effects, metabolism, pathology)
- Blotting, Western
- Brain
(pathology)
- Dimethyl Fumarate
- Encephalomyelitis, Autoimmune, Experimental
(metabolism, pathology)
- Extracellular Signal-Regulated MAP Kinases
(metabolism)
- Fumarates
(pharmacology)
- Inflammation
(prevention & control)
- Interleukin-1beta
(antagonists & inhibitors)
- Interleukin-6
(antagonists & inhibitors)
- Microglia
(drug effects, metabolism, pathology)
- Nitric Oxide
(biosynthesis)
- Nitric Oxide Synthase Type II
(antagonists & inhibitors)
- Nitrites
(metabolism)
- Rats, Wistar
- Reverse Transcriptase Polymerase Chain Reaction
- RNA, Messenger
(biosynthesis, genetics)
- Tumor Necrosis Factor-alpha
(antagonists & inhibitors)
- NF-E2-Related Factor 2
(biosynthesis, genetics)
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