Tumor necrosis factor alpha and interferon gamma cooperatively induce oxidative stress and motoneuron death in rat spinal cord embryonic explants
| Autor: | Laia Tolosa, Víctor J. Asensio, R.M. Soler, Margalida Mir, M. Gou-Fabregas, Gabriel Olmos, Jerònia Lladó |
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| Rok vydání: | 2009 |
| Předmět: |
Cell Survival
medicine.medical_treatment Apoptosis Nitric Oxide Proinflammatory cytokine Rats Sprague-Dawley Tissue Culture Techniques chemistry.chemical_compound Interferon-gamma Cell Movement medicine Animals Interferon gamma Neuroinflammation Motor Neurons biology Microglia Tumor Necrosis Factor-alpha General Neuroscience Embryo Mammalian Cell biology Culture Media Rats Nitric oxide synthase Oxidative Stress Cytokine medicine.anatomical_structure chemistry Spinal Cord Immunology biology.protein Tumor necrosis factor alpha Nicotinamide adenine dinucleotide phosphate medicine.drug |
| Zdroj: | Neuroscience. 162(4) |
| ISSN: | 1873-7544 |
| Popis: | The accumulation of reactive microglia in the degenerating areas of amyotrophic lateral sclerosis (ALS) tissue is a key cellular event creating a chronic inflammatory environment that results in motoneuron death. We have developed a new culture system that consists in rat spinal cord embryonic explants in which motoneurons migrate outside the explant, growing as a monolayer in the presence of glial cells. The proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) have been proposed to be involved in ALS-linked microglial activation. In our explants, the combined exposure to these cytokines resulted in an increased expression of the pro-oxidative enzymes inducible nitric oxide synthase (iNOS), the catalytic subunit of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, gp91(phox) and cyclooxygenase-2 (COX-2), as compared to each cytokine alone. This effect was related to their cooperation in the activation of the transcription factor nuclear factor kappa B (NF-kappaB). TNF-alpha and IFN-gamma also cooperated to promote protein oxidation and nitration, thus increasing the percentage of motoneurons immunoreactive for nitrotyrosine. Apoptotic motoneuron death, measured through annexin V-Cy3 and active caspase-3 immunoreactivities, was also found cooperatively induced by TNF-alpha and IFN-gamma. Interestingly, these cytokines did not affect the viability of purified spinal cord motoneurons in the absence of glial cells. It is proposed that the proinflammatory cytokines TNF-alpha and IFN-gamma have cooperative/complementary roles in inflammation-induced motoneuron death. |
| Databáze: | OpenAIRE |
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