title: Cellular localization and temporal elevation of tumor necrosis factor-alpha, interleukin-1 alpha, and transforming growth factor-beta 1 mRNA in hippocampal injury response induced by trimethyltin.
abstract: In certain pathologic states, cytokine production may become spatially and temporally dysregulated, leading to their inappropriate production and potentially detrimental consequences. Tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1, IL-6, and transforming growth factor-beta (TGF-beta) mediate a range of host responses affecting multiple cell types. To study the role of cytokines in the early stages of brain injury, we examined alterations in the 17-day-old mouse hippocampus during trimethyltin-induced neurodegeneration characterized by neuronal necrosis, microglia activation in the dentate, and astrocyte reactivity throughout the hippocampus. By 24 h after dosing, elevations in mRNA levels for TNF-alpha, IL-1alpha, IL-1beta, and IL-6 mRNA were seen. TGF-beta1 mRNA was elevated at 72 h. In situ hybridization showed that TNF-alpha and IL-1alpha were localized to the microglia, whereas TGF-beta1 was expressed predominantly in hippocampal pyramidal cells. Intercellular adhesion molecule-1, EB-22, Mac-1, and glial fibrillary acidic protein mRNA levels were elevated within the first 3 days of exposure in the absence of increased inducible nitric oxide synthetase and interferon-gamma mRNA. These data suggest that pro-inflammatory cytokines contribute to the progression and pattern of neuronal degeneration in the hippocampus.
authors.affiliation: Laboratory of Neurotoxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 17709, USA.
authors.forename: A
authors.initials: A
authors.lastname: Bruccoleri
authors.forename: H
authors.initials: H
authors.lastname: Brown
authors.forename: G J
authors.initials: GJ
authors.lastname: Harry
mesh_terms: D000818:Animals; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism*; D012260:Ribonucleases / Q000378:metabolism; D016708:Synaptophysin / Q000032:analysis; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D014298:Trimethyltin Compounds / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: D007375:Interleukin-1; D012333:RNA, Messenger; D016708:Synaptophysin; D016212:Transforming Growth Factor beta; D014298:Trimethyltin Compounds; D014409:Tumor Necrosis Factor-alpha; C046488:trimethyltin; D012260:Ribonucleases