Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:017444 (TNF)
 61,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent investigations have demonstrated a local inflammatory response in Alzheimer's disease (AD), including microglia and cytokines. Levels of the cytokine tumor necrosis factor alpha (TNF-alpha) in sera from patients with AD and age-matched controls were measured by an enzyme-linked immunoassay and a cytotoxicity bioassay. Significantly elevated levels of TNF were found in AD sera compared to controls. Elevated circulating TNF may be derived from the local CNS inflammatory reaction in AD, and may account for some systemic manifestations of AD such as weight loss. Future studies may determine if, in the absence of complicating disorders which may elevate TNF, circulating TNF could be a marker of AD inflammatory activity.
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PMID:Elevated circulating tumor necrosis factor levels in Alzheimer's disease. 174 13

Multiple sclerosis (MS) brain tissue, spleen, and PBMC were studied using immunocytochemistry and FACS for immunoreactivity for lymphotoxin (LT) and TNF. Both cytokines were identified in acute and chronic active MS lesions but were absent from chronic silent lesions. LT was associated with CD3+ lymphocytes and Leu-M5+ microglia cells at the lesion edge and to a lesser extent, in adjacent white matter. TNF was associated with astrocytes in all areas of the lesion, and with foamy macrophages in the center of the active lesion. In acute lesions, immunoreactivity for TNF in endothelial cells was noted at the lesion edge. No LT or TNF reactivity was detected in Alzheimer's or Parkinson's disease brain tissues but was present at lower levels in central nervous system (CNS) tissue from other inflammatory conditions, except for adrenoleucodystrophy which displayed high levels of LT in microglia. No increase in LT and TNF reactivity was detected in spleen and PBMC of MS patients suggesting specific reactivity within the CNS. These results indicate that LT and TNF may be involved in the immunopathogenesis of MS, and can be detected in both inflammatory cells and cells endogenous to the CNS.
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PMID:Identification of lymphotoxin and tumor necrosis factor in multiple sclerosis lesions. 199 3

Frozen brain specimens from patients with multiple sclerosis (MS) and other neurologic diseases were analyzed using immunocytochemical techniques for the presence of TNF. In brain lesions in MS, and subacute sclerosing panencephalitis, TNF+ cells were demonstrated. At the lesion site in MS, TNF+ staining is associated with both astrocytes and macrophages. These observations were not made in Alzheimer's disease or normal brain tissue. The presence of TNF in MS lesions suggests a significant role for cytokines and the immune response in disease progression.
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PMID:Tumor necrosis factor identified in multiple sclerosis brain. 275 93

A number of hypotheses regarding the pathogenesis of scrapie and other human and animal spontaneous and experimental subacute spongiform encephalopathies (SSE) are presented here. In particular, it is speculated that a PrPsc 27-30-induced suppression of host's defense system is responsible, through the existence of the different and synergistically operating mechanisms, for the absence of any documented inflammatory or immunologic response during SSE. This could be therapeutically counterparted by the utilization of cytokines (TNF, IL-1, etc) or cytokine-inducers, provided that synthesis and secretion of the above inflammation mediators on behalf of reticulo-endothelial cells were strongly depressed by PrP 27-30, as suggested. Finally, some hypotheses are also made in relation to the blood-brain-barrier's integrity in susceptible hosts. Similarly to Alzheimer's disease (AD) in man, this could play a role also in SSE pathogenesis, facilitating cerebral localization of metals such as aluminum, lead, or silica, which have already been shown to enhance amyloid fibrils' polymerization and deposition within human brain tissue.
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PMID:Amyloid, amyloid-inducers, cytokines and heavy metals in scrapie and other human and animal subacute spongiform encephalopathies: some hypotheses. 829 2

CDP-choline was given to patients with Alzheimer's disease (AD) at a daily dose of 1000 mg/day p.o. for one month. This compound slightly improved mental performance, tended to reduce theta activity in fronto-temporal regions, increasing alpha power in occipital areas, and enhanced cerebrovascular perfusion by increasing blood flow velocity and reducing pulsatility and resistance indexes. In addition, CDP-choline diminished histamine and interleukin-1 levels in blood and serum, respectively, and increased plasma TNF.
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PMID:Therapeutic effects of CDP-choline in Alzheimer's disease. Cognition, brain mapping, cerebrovascular hemodynamics, and immune factors. 862 20

Cytokines such as interleukin-1 (IL-1) and interleukin-6 (IL-6) have previously been shown to participate in neurodegenerative processes including Alzheimer's disease. However, the molecular consequences of increased cytokine expression in the brain remain largely unknown. We have studied the effects of IL-1, IL-6 and TNF alpha on the expression of the acute-phase protein alpha 1-antichymotrypsin (ACT) in human astrocytoma cell lines. Both IL-1 and TNF alpha, but not IL-6, were able to induce ACT gene transcription and protein synthesis. The synthetic glucocorticoid dexamethasone enhanced cytokine-induced ACT mRNA expression and protein synthesis. We conclude that IL-1-induced expression of ACT may be part of the inflammatory response in the brain and may be involved in the pathology of Alzheimer's disease.
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PMID:IL-1 beta and TNF alpha, but not IL-6, induce alpha 1-antichymotrypsin expression in the human astrocytoma cell line U373 MG. 874 37

The deposition of beta-amyloid peptides in the brain in form of senile plaque is the key event responsible for Alzheimer pathology. Among various mechanisms that have been proposed to explain the neurotoxicity of beta-amyloid deposits, a new one, recently identified in our laboratory, suggests that beta-amyloid peptides may be indirectly toxic for neurons by activating microglial cells to produce NO (2). We have investigated if astrocytes, nerve cells that play an important role in many brain diseases, also might be involved in a similar mechanism of neuronal damage. The results have demonstrated that (1) beta-amyloid peptide (25-35), in the presence of IFN gamma or TNF alpha, induces the production of NO in the astrocyte cell line C6, while neither cytokine was effective per se; (2) NO generation is also synergically induced by beta-amyloid peptide (25-35) in the presence of IL-1 beta, the latter being a cytokine able to activate astrocytes per se; (3) the effect of beta-amyloid peptide (25-35) is due to the induction of the expression of the gene of inducible NO-synthase. These findings suggest that astrocytes, activated by deposited beta-amyloid peptides and cytokines, may play a role in neuronal damage via the indirect NO mechanism.
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PMID:Synergistic induction of nitric oxide by beta-amyloid and cytokines in astrocytes. 875 86

The protease inhibitor alpha 1-antichymotrypsin (ACT) has been suggested to be involved in the etiology of Alzheimer's disease (AD). Increased levels of ACT have been found in serum and brains of AD patients, and ACT has been proposed to regulate beta-amyloid fibril formation in vitro. To gain insight into the regulation of ACT in the brain, we investigated the signal transduction pathways involved in ACT gene expression and protein synthesis in the human astrocytoma cell line U373. This cell line has previously been shown to respond with strong ACT synthesis on stimulation with interleukin-1 beta (IL-1 beta) or tumor necrosis factor-alpha (TNF alpha). Here, we describe that both IL-1 beta and TNF alpha activate the transcription factor nuclear factor-kappa B (NF-kappa B) via production of reactive oxygen intermediates resulting in ACT expression. In addition, we show that neither protein kinase C nor protein kinase A is involved in IL-1 beta- or TNF alpha-induced ACT expression. These results suggest that activation of NF-kappa B may be one possible cause of increased ACT levels in AD and provide a basis for the development of drugs used for the modulation of inflammatory processes occurring in AD.
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PMID:Interleukin-1 beta and tumor necrosis factor-alpha induce expression of alpha 1-antichymotrypsin in human astrocytoma cells by activation of nuclear factor-kappa B. 886 11

The original notion that the brain represented an "immune-privileged" organ lacking the capability to produce an inflammatory response to an injury, would appear no longer tenable. Indeed, accumulating evidence during the last decade has shown that the CNS can mount a well-defined inflammatory response to a variety of insults including trauma, ischemia, transplantation, viral infections, toxins as well as neurodegenerative processes. Many aspects of this centrally-derived inflammatory response parallel, to some extent, the nature of such a reaction in the periphery. Through the recent application of molecular biological techniques, new concepts are rapidly emerging as to the molecular mechanisms associated with the development of brain injury. In particular, the importance of cytokines, especially TNF alpha and IL-1 beta, as well as adhesion molecules, has been emphasized in the propagation and maintenance of a CNS inflammatory response. This review will summarize recent observations as to the involvement of these inflammatory mediators in CNS injury and lay claim to the possibility that inhibitors of peripheral inflammation may also be of benefit in treating CNS injuries such as stroke, head trauma, Alzheimer's disease and multiple sclerosis.
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PMID:The role of inflammation and cytokines in brain injury. 888 Jul 34

Possible roles of the complement (C) system in the normal and injured brain were explored with inbred mice that carried a frameshift mutation in the C5 gene. A congenic pair was used: the C5-sufficient (C5+) B10.D2/nSnJ strain with the functional allele (Hc1) from the C57BL/10J donor strain was compared with the C5-deficient (C5-) B10.D2/oSnJ with the Hc0 allele from the C5-deficient DBA/2J donor strain. In response to the excitotoxin kainic acid (KA), C5- mice had more hippocampal pyramidal neuron death and greater induction of astrocyte mRNAs (GFAP, apoE, apoJ). In primary astrocyte cultures from unlesioned mice, an inflammatory stimulus (LPS) caused greater production of IL-6 and TNF production in C5- mice. These enhanced responses to KA and LPS suggest that hereditary C5 deficits modify responses to neurodegenerative stimuli of neurons and astrocytes. Moreover, unlesioned C5- mice had smaller input-output slopes for the NMDA component of the EPSP amplitude, but enhanced the Ca(+2)-dependent AMPA binding. Thus, C5 deficits also modify basal properties of glutamatergic neurotransmission that pertain to synaptic plasticity. These findings are also discussed in relation to roles of the C-system in Alzheimer disease (AD). C5 deficiencies may also be considered in the choice of strains as transgene hosts and for genetic analysis of normal and pathological brain functions. In recent transgenic studies for AD, C5- hosts showed greater neurodegeneration, consistent with the present data. These pleiotropic associations of C5 deficiency indicate roles for the C-system in neurodegeneration, but also in normal neural functions.
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PMID:Hereditary deficiencies in complement C5 are associated with intensified neurodegenerative responses that implicate new roles for the C-system in neuronal and astrocytic functions. 898 20


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