Cytokine production, glutamate release and cell death in rat cultured astrocytes treated with unconjugated bilirubin and LPS.
In hyperbilirubinemic newborns, sepsis is considered a risk factor for kernicterus. Evidence shows that injury to astrocytes triggers cytokine release. We examined the effects of unconjugated bilirubin (UCB) alone, or in combination with LPS, on the release of glutamate and cytokines from astrocytes in conditions inducing less than 10% of cell death. UCB leads to an increase of extracellular glutamate and highly enhances the release of TNF-alpha and IL-1beta, while inhibiting the production of IL-6. LPS potentiates immunostimulatory properties of UCB. These results point out the role of cytokines and provide a basis for the significance of sepsis in UCB encephalopathy.
Fernandes
Adelaide
A
Centro de Patogénese Molecular (UBMBE), Faculdade de Farmácia, University of Lisbon, Av. Forças Armadas, 1600-083 Lisbon, Portugal.
Silva
Rui F M
RF
Falcão
Ana S
AS
Brito
Maria A
MA
Brites
Dora
D
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D001663:Bilirubin / Q000494:pharmacology*; D001921:Brain / Q000166:cytology; D016923:Cell Death / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D018698:Glutamic Acid / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051381:Rats
D016207:Cytokines; D008070:Lipopolysaccharides; D018698:Glutamic Acid; D007770:L-Lactate Dehydrogenase; D001663:Bilirubin