title: Dexamethasone reduces bilirubin-induced toxicity and IL-8 and MCP-1 release in human NT2-N neurons.
abstract: The mechanisms of neurotoxicity induced by unconjugated bilirubin (UCB) in newborns are incompletely understood. UCB may cause both necrotic and apoptotic neuronal death. We explored UCB toxicity and release of cytokines in human NT2-N neurons and the effect of dexamethasone on these processes. Cultured NT2-N neurons were exposed to UCB, and neuronal damage was evaluated by LDH release and MTT cleavage. After 96 hours, 2 μM UCB significantly increased release of IL-8 and MCP-1, but not IL-13, IP-10, PDGF, or VEGF. Dexamethasone significantly lowered the UCB-induced increase in MCP-1 release, and attenuated UCB-induced neuronal damage assessed with MTT cleavage and LDH release. For comparison, the effects of hydrogen peroxide on cytokine formation and neuronal damage were tested. Hydrogen peroxide increased MCP-1, IP-10, and VEGF, but not IL-8, IL-13, or PDGF. Dexamethasone inhibited the hydrogen peroxide-induced increase in MCP-1 and IP-10. We conclude that UCB causes release of IL-8 and MCP-1 in cultured human NT2-N neurons. Dexamethasone reduces UCB-induced cytokine release and protects against UCB-induced toxicity.
authors.affiliation: Department of Pediatric Research, Oslo University Hospital Rikshospitalet, N-0027 Oslo, Norway. runar.almaas@ous-hf.no
authors.forename: Runar
authors.initials: R
authors.lastname: Almaas
authors.forename: Erik
authors.initials: E
authors.lastname: Hankø
authors.forename: Tom Eirik
authors.initials: TE
authors.lastname: Mollnes
authors.forename: Terje
authors.initials: T
authors.lastname: Rootwelt
mesh_terms: D001663:Bilirubin / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology*; D006801:Humans; D016209:Interleukin-8 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016209:Interleukin-8; D003907:Dexamethasone; D001663:Bilirubin