title: Interleukin-6-induced S100B secretion is inhibited by haloperidol and risperidone.
abstract: Although inflammation may be a physiological defense process, imbalanced neuroinflammation has been associated with the pathophysiology of brain disorders, including major depression and schizophrenia. Activated glia releases a variety of pro-inflammatory cytokines that contribute to neuronal dysfunction. Elevated levels of S100B, a glia derived protein, have been observed in the serum and CSF of schizophrenic patients suggesting a glial role in the disease. We evaluated whether S100B secretion (in C6 glioma cells and hippocampal slices in Wistar rats) could be directly modulated by the main inflammatory cytokines (IL-1β, TNF-α, IL-6 and IL-8) altered in schizophrenia, as well as the possible involvement of mitogen-activated protein kinase (MAPK) pathways in these responses. We also investigated the effects of typical and atypical antipsychotic drugs on glial cytokine-induced S100B release. Our results suggest that S100B secretion is increased by pro-inflammatory cytokines via MAPK and that oxidative stress may be a component of this modulation. These results reinforce the idea that the S100B protein is involved in the inflammatory response observed in many brain diseases, including schizophrenia. Moreover the antipsychotics, haloperidol and risperidone, were able to inhibit the secretion of S100B following IL-6 stimulation in C6 glioma cells.
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos, 2600-Anexo, 90035-003, Porto Alegre, Brazil.
authors.forename: Daniela Fraga
authors.initials: DF
authors.lastname: de Souza
authors.forename: Krista
authors.initials: K
authors.lastname: Wartchow
authors.forename: Fernanda
authors.initials: F
authors.lastname: Hansen
authors.forename: Paula
authors.initials: P
authors.lastname: Lunardi
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Guerra
authors.forename: Patrícia
authors.initials: P
authors.lastname: Nardin
authors.forename: Carlos-Alberto
authors.initials: CA
authors.lastname: Gonçalves
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005910:Glioma / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology*; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism*; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D018967:Risperidone / Q000494:pharmacology*; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000378:metabolism*; D013778:Tetrazolium Salts; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000093242:Interleukin-6 Inhibitors
chemical_list: D014150:Antipsychotic Agents; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D005978:Glutathione; D006220:Haloperidol; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D007770:L-Lactate Dehydrogenase; D009414:Nerve Growth Factors; D009569:Nitric Oxide; D017382:Reactive Oxygen Species; D018967:Risperidone; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D013778:Tetrazolium Salts; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C579158:S100b protein, rat; C022616:thiazolyl blue