Interferon-beta is neuroprotective against the toxicity induced by activated microglia.
Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system characterized by demyelination, T lymphocyte infiltration, and neuronal degeneration. Interferon-beta (IFN)-beta reduces symptoms of the relapsing-remitting form of MS. In this study, we investigated whether IFN-beta is neuroprotective against the toxicity induced by activated microglia in cortical neurons and microglia co-cultures. IFN-beta suppressed the production of glutamate and superoxide by activated microglia to 70% and 75% of lipopolysaccharide stimulation, respectively, and prevented microglial-induced neuronal cell death. Although IFN-beta enhanced the production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and nitric oxide (NO) by activated microglia, these molecules did not directly induce neurotoxicity in cultured cortical neurons. IFN-beta did not prevent neuronal cell death induced by the peroxynitrite donor 3-morpholinosydnonimine (SIN-1) or ionotropic glutamate receptor agonists such as N-methyl-D-aspartic acid (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). These results suggest that IFN-beta may be a useful agent counteracting neurotoxicity associated with activated microglia.
Jin
Shijie
S
Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8601, Japan.
Kawanokuchi
Jun
J
Mizuno
Tetsuya
T
Wang
Jinyan
J
Sonobe
Yoshifumi
Y
Takeuchi
Hideyuki
H
Suzumura
Akio
A
D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D007370:Interferon Type I / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents; D009569:Nitric Oxide / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000378:metabolism; D011247:Pregnancy; D011994:Recombinant Proteins; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D018690:Excitatory Amino Acid Agonists; D007370:Interferon Type I; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D018698:Glutamic Acid; C002385:linsidomine; D016202:N-Methylaspartate; D008981:Molsidomine