Proinflammatory cytokine production by cultured neonatal rat microglia after exposure to blood products.
Periventricular germinal matrix hemorrhage is a devastating complication of preterm birth. Inflammation appears to play a role in brain damage after premature birth and hypoxia. The effects of rat blood plasma and serum on cytokine expression by cultured rat microglial cells were investigated. We analyzed mRNA expression levels of tumor necrosis factor (TNF)-alpha, interleukin-6 and protease activated receptor-1 and -4 by quantitative RT-PCR. Protein expression for TNFalpha was done using immunocytochemistry and ELISPOT assays. Plasma and serum had dose dependent toxic effects on microglia as measured by lactate dehydrogenase release assay and activated caspase-3 immunocytochemistry. High concentrations of plasma enhanced TNFalpha mRNA expression and protein production, while high concentrations of serum enhanced IL-6 mRNA expression. This study suggests that soluble components of blood might be differentially responsible for up regulating production of the cytokines TNFalpha and IL-6 by microglia from immature rodent brain.
Juliet
Packiasamy A R
PA
Department of Pathology, University of Manitoba and Manitoba Institute of Child Health, Canada.
Mao
Xiaoyan
X
Del Bigio
Marc R
MR
D000818:Animals; D000831:Animals, Newborn; D001720:Birth Injuries / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D001798:Blood Proteins / Q000276:immunology* / Q000494:pharmacology; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002543:Cerebral Hemorrhage / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004660:Encephalitis / Q000209:etiology / Q000276:immunology* / Q000378:metabolism; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D017628:Microglia / Q000276:immunology* / Q000378:metabolism*; D047928:Premature Birth / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D044463:Receptor, PAR-1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D044462:Receptors, Proteinase-Activated / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics / Q000276:immunology
D001798:Blood Proteins; D016207:Cytokines; D015850:Interleukin-6; D012333:RNA, Messenger; D044463:Receptor, PAR-1; D044462:Receptors, Proteinase-Activated; D014409:Tumor Necrosis Factor-alpha; C481942:protease-activated receptor 4, mouse; D007770:L-Lactate Dehydrogenase; D053148:Caspase 3