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Cytokines in neuroimmunomodulation and neuropathology: Dual expression of the p80 type I and p68 type II interleukin-1 receptors on murine growth hormone producing cells. Murine neurovirulent retrovirus ts-1-MoMulV induces tumor necrosis factor-alpha and nitric oxide secretion from glial cultures in vitro

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Title: Cytokines in neuroimmunomodulation and neuropathology: Dual expression of the p80 type I and p68 type II interleukin-1 receptors on murine growth hormone producing cells. Murine neurovirulent retrovirus ts-1-MoMulV induces tumor necrosis factor-alpha and nitric oxide secretion from glial cultures in vitro
Author(s): French, Richard Alan
Doctoral Committee Chair(s): Zachary, James F.
Department / Program: Pathobiology
Discipline: Pathobiology
Degree Granting Institution: University of Illinois at Urbana-Champaign
Degree: Ph.D.
Genre: Dissertation
Subject(s): Biology, Neuroscience Biology, Cell Health Sciences, Pathology Biology, Veterinary Science Health Sciences, Immunology
Abstract: Inflammatory cytokines, interleukin 1 (IL-1$\alpha,$ IL-1$\beta$) and tumor necrosis factor (TNF-$\alpha),$ are coordinators of the immune and inflammatory responses but also play a critical regulatory role in brain development, function, disease and regulation of the neuroendocrine immune axis. In the latter context, inflammatory cytokines modulate the synthesis and secretion of various pituitary hormones including growth hormone (GH) and adrenocorticotropic hormone (ACTH). IL-1$\alpha$ and IL-1$\beta$ exert their effects by interaction with two distinct receptors, p80 IL-1R and p68 IL-1R. We have used immunohistochemistry to demonstrate the cellular localization and dual expression of the IL-1R isoforms in the murine adenohypophysis. In conjunction with previous studies demonstrating high affinity binding sites for IL-1$\alpha,$ expression of the p80 and p68 IL-1R mRNA, and the identification of the p80 IL-1R protein in the adenohypophysis, we have shown that expression of the p80 and p68 IL-1R proteins is restricted to predominantly those cells that synthesize GH, and that there is expression of both IL-1R isoforms on the same cell population. These findings corroborate the role of GH in the neuroendocrine immune axis and suggest that IL-1 mediated GH release is regulated, in part, at the level of the pituitary and is finely regulated.Neurovirulent ts1 MoMuLV is an animal model for motor neuron and neurodegenerative diseases such as amyotrophic lateral sclerosis and AIDS dementia complex (ADC). Our studies have identified a potential indirect mechanism for neuronal degeneration similar to the proposed neuropathogenesis of ADC. Resident CNS microglial cells are the principal cell target for ts1 MoMuLV infection and neurons are "innocent" bystander cells indirectly affected by activation of the microglial cells. Results indicate that induction of TNF-$\alpha$ (bioassay, WEHI 164 cells, $217\pm15$ pg TNF-$\alpha$/ml/10$\sp5$ microglial cells; ELISA $577\pm100$ pg TNF-$\alpha$ml/10$\sp5$ microglial cells), and nitric oxide (NO) are associated with glial cell infection by ts1 MoMuLV. The findings suggest that ts1 MoMuLV neurotoxicity in the murine retroviral neuroimmunodegenerative disease may be associated with the induction of TNF-$\alpha$ and/or NO.
Issue Date: 1996
Type: Text
Language: English
URI: http://hdl.handle.net/2142/20192
ISBN: 9780591087901
Rights Information: Copyright 1996 French, Richard Alan
Date Available in IDEALS: 2011-05-07
Identifier in Online Catalog: AAI9702518
OCLC Identifier: (UMI)AAI9702518
 

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