Norepinephrine protects cortical neurons against microglial-induced cell death.
Interleukin-1 beta (IL-1beta) is one of the main cytokines involved in the inflammatory response; it has multiple effects that can contribute to cell damage, one of which is the upregulation of the inducible form of nitric oxide (NO) synthase (NOS2) in certain cell types. We demonstrated previously that in vivo, cortical microglial inflammatory responses were increased when noradrenaline (NE) levels were depleted, suggesting that NE can reduce microglial activation. In the present report, we examined the role of IL-1beta in neurotoxicity induced by microglial-conditioned media, and possible neuroprotective effects of NE. Incubation of cortical neurons with conditioned media (CM) obtained from lipopolysaccharide (LPS)-treated microglia induced neuronal NOS2 expression and increased neuronal cell death, and these responses were reduced if the neurons were coincubated with interleukin-1 receptor antagonist. Cotreatment of microglial cells with LPS plus NE potently blocked IL-1beta production and reduced the ability of the CM to induce neuronal NOS2 and cell death. These results suggest that microglial release of IL-1beta is an important activator of neuronal inflammatory responses, and that protective effects of NE upon neurons involve a reduction of microglial-derived IL-1beta.
Madrigal
Jose L M
JL
Department of Anesthesiology, University of Illinois, Chicago, Illinois 60612, USA.
Feinstein
Douglas L
DL
Dello Russo
Cinzia
C
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004622:Embryo, Mammalian; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D017628:Microglia / Q000187:drug effects / Q000502:physiology*; D008954:Models, Biological; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009638:Norepinephrine / Q000494:pharmacology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins / Q000494:pharmacology; D013997:Time Factors; D014230:Triazoles / Q000494:pharmacology
C488155:3-amino-5-mercapto-1,2,4-triazole; D017077:Culture Media, Conditioned; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D012795:Sialoglycoproteins; D014230:Triazoles; D009569:Nitric Oxide; D007770:L-Lactate Dehydrogenase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D010751:Phosphopyruvate Hydratase; D009638:Norepinephrine