The Experts below are selected from a list of 201 Experts worldwide ranked by ideXlab platform
Mark P Mattson - One of the best experts on this subject based on the ideXlab platform.
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brain injury and Tumor Necrosis Factors induce calbindin d 28k in astrocytes evidence for a cytoprotective response
Journal of Neuroscience Research, 1995Co-Authors: Mark P Mattson, Bin Cheng, S A Baldwin, V L Smithswintosky, Jeffery N Keller, James W Geddes, Stephen W Scheff, S ChristakosAbstract:Calbindin is a 28 kDa calcium-binding protein expressed in restricted neuronal populations in the mammalian brain where it may play a role in protecting neurons against excitotoxic insults. Recent findings indicate that electrical activity and some neurotrophic Factors can induce the expression of calbindin in neurons. We now report that brain injury, effected by systemic administration of the excitotoxin kainate or mechanical trauma, induces expression of calbindin in cells of the corpus callosum and subcortical white matter. Immunohistochemical analysis using antibodies to the astrocyte-specific proteins (glial fibrillary acidic protein and S-100β) established the identity of calbindin immunoreactive cells as astrocytes. Because brain injury is known to induce the expression of several neurotrophic Factors and cytokines, we employed cultures of hippocampal and neocortical astrocytes to test the hypothesis that such Factors can induce expression of calbindin in astrocytes. Tumor Necrosis Factors (TNFβ and TNFβ), cytokines that are expressed in response to brain injury, induced the expression of calbindin in cultured rat hippocampal and neocortical astrocytes. Two neurotrophic Factors, basic fibroblast growth factor and nerve growth factor, did not induce calbindin in astrocytes. TNF-treated, calbindin-expressing astrocytes were resistant to acidosis and calcium ionophore toxicity, suggesting that TNFs and calbindin may serve a cytoprotective role in astrocytes in the injured brain. © 1995 Wiley-Liss, Inc.
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Tumor Necrosis Factors alpha and beta protect neurons against amyloid beta peptide toxicity evidence for involvement of a kappa b binding factor and attenuation of peroxide and ca2 accumulation
Proceedings of the National Academy of Sciences of the United States of America, 1995Co-Authors: Steven W Barger, Dorothee Horster, Katsutoshi Furukawa, Yadong Goodman, Josef Krieglstein, Mark P MattsonAbstract:In Alzheimer disease (AD) the amyloid beta-peptide (A beta) accumulates in plaques in the brain. A beta can be neurotoxic by a mechanism involving induction of reactive oxygen species (ROS) and elevation of intracellular free calcium levels ([Ca2+]i). In light of evidence for an inflammatory response in the brain in AD and reports of increased levels of Tumor Necrosis factor (TNF) in AD brain we tested the hypothesis that TNFs affect neuronal vulnerability to A beta. A beta-(25-35) and A beta-(1-40) induced neuronal degeneration in a concentration- and time-dependent manner. Pretreatment of cultures for 24 hr with TNF-beta or TNF-alpha resulted in significant attenuation of A beta-induced neuronal degeneration. Accumulation of peroxides induced in neurons by A beta was significantly attenuated in TNF-pretreated cultures, and TNFs protected neurons against iron toxicity, suggesting that TNFs induce antioxidant pathways. The [Ca2+]i response to glutamate (quantified by fura-2 imaging) was markedly potentiated in neurons exposed to A beta, and this action of A beta was suppressed in cultures pretreated with TNFs. Electrophoretic mobility-shift assays demonstrated an induction of a kappa beta-binding activity in hippocampal cells exposed to TNFs. Exposure of cultures to I kappa B (MAD3) antisense oligonucleotides, a manipulation designed to induce NF-kappa B, mimicked the protection by TNFs. These data suggest that TNFs protect hippocampal neurons against A beta toxicity by suppressing accumulation of ROS and Ca2+ and that kappa B-dependent transcription is sufficient to mediate these effects. A modulatory role for TNF in the neurodegenerative process in AD is proposed.
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Tumor Necrosis Factors protect neurons against metabolic excitotoxic insults and promote maintenance of calcium homeostasis
Neuron, 1994Co-Authors: Bin Cheng, Sylvia Christakos, Mark P MattsonAbstract:Emerging data indicate that neurotrophic Factors and cytokines utilize similar signal transduction mechanisms. Although neurotrophic Factors can protect CNS neurons against a variety of insults, the role of cytokines in the injury response is unclear. We now report that TNF beta and TNF alpha (1-100 ng/ml) can protect cultured embryonic rat hippocampal, septal, and cortical neurons against glucose deprivation-induced injury and excitatory amino acid toxicity. The elevation of intracellular calcium concentration ([Ca2+]i) induced by glucose deprivation, glutamate, NMDA, or AMPA was attenuated in neurons pretreated with TNF beta. The mechanism whereby TNFs stabilize [Ca2+]i may involve regulation of the expression of proteins involved in maintaining [Ca2+]i homeostasis, since both TNF beta and TNF alpha caused a 4- to 8-fold increase in the number of neurons expressing the calcium-binding protein calbindin-D28k. These data suggest a neuroprotective role for TNFs in the brain's response to injury.
Gregory R Mundy - One of the best experts on this subject based on the ideXlab platform.
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preferential inhibition of cytokine stimulated bone resorption by recombinant interferon gamma
Journal of Bone and Mineral Research, 2009Co-Authors: Maxine Gowen, Glenn Evan Nedwin, Gregory R MundyAbstract:It is likely that immune cells in the bone marrow produce Factors which are involved in the local control of bone remodeling. Immune cell products such as interleukin-1 and the Tumor Necrosis Factors are potent stimulators of bone resorption in vitro. In this paper, we have studied the effects of recombinant murine interferonγ on bone resorption stimulated by these agents and the systemic calcium-regulating hormones 1,25(OH)2 vitamin D3 and parathyroid hormone. We found that interferon-7 completely abolished bone resorption stimulated by the cytokines interleukin-1, Tumor Necrosis factor α and Tumor Necrosis factor s. In contrast, parathyroid hormone- and 1,25(OH)2 vitamin D3-stimulated bone resorption were not significantly affected by the addition of interferon-γ under the same conditions. Parathyroid hormone-stimulated bone resorption was inhibited slightly when larger concentrations of interferon-γ were used for more prolonged periods. The inhibitory effects on cytokine-stimulated bone resorption occurred at interferon concentrations of 100 U/ml (half-maximal) to 300 U/ml (complete inhibition). This relatively selective inhibition of cytokine-stimulated bone resorption by an immune cell product may have physiological significance in the local control of trabecular bone volume and bone remodeling.
Christopher J Secombes - One of the best experts on this subject based on the ideXlab platform.
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functional characterisation of the recombinant Tumor Necrosis Factors in rainbow trout oncorhynchus mykiss
Developmental and Comparative Immunology, 2003Co-Authors: Jun Zou, Scott Peddie, Giuseppe Scapigliati, Yongan Zhang, Niels C Bols, A E Ellis, Christopher J SecombesAbstract:Abstract Tumor Necrosis factor (TNF) is a key mediator in regulating the inflammatory response. Previously two TNF genes have been cloned and sequenced from rainbow trout, Oncorhynchus mykiss . In this study, the mature peptides of the two TNF molecules were produced in bacteria, purified under native conditions and their bioactivities evaluated in vitro. Both trout rTNF1 and rTNF2 induced gene expression of a number of proinflammatory Factors including IL1β, TNF1, TNF2, IL8 and COX2 in freshly isolated head kidney leucocytes and the macrophage cell line RTS11. The stimulatory doses of both rTNFs were ≥10 ng/ml. Moreover, leucocyte migration and phagocytic activity were enhanced in vitro by the rTNFs in a dose dependent manner. Western blot analysis revealed the presence of multiple forms of rTNF structures including monomeric, dimeric and trimeric forms, suggesting that formation of a homotrimeric structure may be essential for the TNF bioactivities.
Maxine Gowen - One of the best experts on this subject based on the ideXlab platform.
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preferential inhibition of cytokine stimulated bone resorption by recombinant interferon gamma
Journal of Bone and Mineral Research, 2009Co-Authors: Maxine Gowen, Glenn Evan Nedwin, Gregory R MundyAbstract:It is likely that immune cells in the bone marrow produce Factors which are involved in the local control of bone remodeling. Immune cell products such as interleukin-1 and the Tumor Necrosis Factors are potent stimulators of bone resorption in vitro. In this paper, we have studied the effects of recombinant murine interferonγ on bone resorption stimulated by these agents and the systemic calcium-regulating hormones 1,25(OH)2 vitamin D3 and parathyroid hormone. We found that interferon-7 completely abolished bone resorption stimulated by the cytokines interleukin-1, Tumor Necrosis factor α and Tumor Necrosis factor s. In contrast, parathyroid hormone- and 1,25(OH)2 vitamin D3-stimulated bone resorption were not significantly affected by the addition of interferon-γ under the same conditions. Parathyroid hormone-stimulated bone resorption was inhibited slightly when larger concentrations of interferon-γ were used for more prolonged periods. The inhibitory effects on cytokine-stimulated bone resorption occurred at interferon concentrations of 100 U/ml (half-maximal) to 300 U/ml (complete inhibition). This relatively selective inhibition of cytokine-stimulated bone resorption by an immune cell product may have physiological significance in the local control of trabecular bone volume and bone remodeling.
Ulf H. Lerner - One of the best experts on this subject based on the ideXlab platform.
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Tumor Necrosis Factors α and β can stimulate bone resorption in cultured mouse calvariae by a prostaglandin independent mechanism
Journal of Bone and Mineral Research, 2009Co-Authors: Ulf H. Lerner, Acke OhlinAbstract:Human recombinant Tumor Necrosis Factors alpha and beta (TNF-alpha and TNF-beta), at and above 1 ng/ml (approximately equal to 70 pM), caused a dose- and time-dependent enhancement of 45Ca release from neonatal mouse calvarial bones in vitro. In addition, TNF-alpha and TNF-beta (3-100 ng/ml) caused a dose-dependent stimulation of prostaglandin E2 (PGE2) formation in the calvarial bones. TNF-alpha also enhanced the biosynthesis of PGI2, as assessed by analysis of the stable breakdown product 6-keto-PGF1 alpha. The stimulatory actions of TNF-alpha and TNF-beta on PGE2 formation was maximal at 12 h. Indomethacin, flurbiprofen, and meclofenamic acid, three structurally unrelated nonsteroidal antiinflammatory drugs, abolished PGE2 biosynthesis induced by TNF-alpha and TNF-beta (100 ng/ml). The 45Ca release stimulated by TNF-alpha and TNF-beta (100 ng/ml), however, was only slightly reduced by indomethacin, flurbiprofen, and meclofenamic acid. The partial inhibitory effect of indomethacin on 45Ca release was seen over a wide range of TNF-alpha concentrations, without affecting the concentration producing half-maximal stimulatory response. TNF-alpha and TNF-beta (100 ng/ml) stimulated bone matrix breakdown, as assessed by analysis of the release of 3H from bone prelabeled with [3H]proline. Also, the stimulatory effect of TNF-alpha and TNF-beta on bone matrix degradation was partially reduced by indomethacin. Hydrocortisone (1 microM) and dexamethasone (0.1 microM) abolished TNF-alpha- and TNF-beta-induced production of PGE2. In contrast to the cyclooxygenase inhibitors, the corticosteroids did not affect the stimulatory action by the cytokines on 45Ca release.(ABSTRACT TRUNCATED AT 250 WORDS)
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Regulation of bone metabolism by the kallikrein-kinin system, the coagulation cascade, and the acute-phase reactants
Oral Surgery Oral Medicine Oral Pathology, 1994Co-Authors: Ulf H. LernerAbstract:Inflammation-induced localized bone resorption in diseases such as marginal and apical periodontitis, rheumatoid arthritis, and osteomyelitis is due to activation and recruitment of osteoclasts by locally produced cytokines and inflammatory mediators. Thus several interleukins (1, 3, 4, 6, and 11), Tumor Necrosis Factors (alpha, beta), colony-stimulating Factors (M and GM), leukemia inhibitory factor, gamma-interferon, and transforming growth factor-beta have effects on bone resorption and bone formation in vivo and in vitro. The kallikrein-kinin system and the coagulation cascade are also activated in inflammation. We have found that peptides produced in the kallikrein-kinin system (bradykinin, kallidin) and thrombin, the end product in the coagulation cascade, can stimulate bone resorption in vitro. The stimulatory effect of bradykinin is linked both to B1 and B2 bradykinin receptors. Both kinins and thrombin stimulate prostaglandin biosynthesis in bone parallel with the bone resorptive effect. The stimulatory effect of bradykinin on bone resorption is completely lost when the prostaglandin response is abolished, whereas thrombin can stimulate bone resorption both via prostaglandin-dependent and independent mechanisms. In addition, bradykinin and thrombin act in concert with interleukin-1 to synergistically stimulate bone resorption and prostaglandin biosynthesis. We also have found that one of the acute-phase reactants, haptoglobin, can stimulate bone resorption in vitro, indicating the possibility of generalized bone loss in chronic inflammatory diseases. Moreover, haptoglobin synergistically potentiates bradykinin-induced and thrombin-induced prostanoid biosynthesis in osteoblasts. These observations indicate that the rate of bone resorption in inflammation-induced bone loss may not be due to a single factor but to the concerted action of several local or systemic Factors.
