Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leukemia inhibitory factor (LIF) and tumor necrosis factor (TNF) have been shown to protect animals from radiation, hyperoxia, and endotoxic shock. TNF is also known to induce the expression of manganese superoxide dismutase (MnSOD) in vitro and in vivo. We therefore examined the effects of these cytokines on reperfusion injury in the isolated rabbit heart model. Rabbits were injected intravenously with 10 micrograms of either human TNF-alpha or lymphotoxin (TNF-beta), or murine TNF-alpha or murine LIF dissolved in saline. Control animals were injected with an equal volume of saline. After 24 h, hearts were isolated and perfused. Following an equilibration period, the hearts were subjected to 1 h ischemia and 1 h of reperfusion. All treated groups showed significant increases in percent recovery of developed tension (% preischemic) when compared to saline-treated control hearts. In addition there were significant decreases in lactate dehydrogenase release (LDH), accumulation of thiobarbituric acid reactive substances (TBARS), and accumulation of carbonyl proteins. These results correlate with increases in myocardial MnSOD activity. Thus, the protection from myocardial reperfusion injury seen in the pretreated group may be due to a mechanism that involves the induction of MnSOD.
J Mol Cell Cardiol 1995 Jan
PMID:Leukemia inhibitory factor and tumor necrosis factor induce manganese superoxide dismutase and protect rabbit hearts from reperfusion injury. 776 Mar 46

The effects of interleukin (IL)-1 beta, IL-4, IL-6, tumor necrosis factor (TNF)-alpha, interferon (IFN)-alpha, IFN-gamma, and transforming growth factor (TGF)-beta 1 on cytochrome P-450 (CYP) 1A expression and polycyclic aromatic hydrocarbon (PAH)-mediated induction in primary human hepatocyte cultures were determined. Most cytokines that were previously found to decrease basal CYP expression could counteract PAH induction of CYP1A mRNA and its associated ethoxyresorufin-O-deethylation (EROD) activity. IL-1 beta and TNF-alpha blocked 3-methylcholanthrene (3-MC)-induced EROD activity by up to 25 and 44%, respectively. IFN-alpha and IFN-gamma antagonized EROD induction by up to 61 and 70%, respectively. TGF-beta 1 proved to be the most effective cytokine, because 72 hr of treatment with 2 ng/ml TGF-beta 1 produced nearly 100% inhibition of 3-MC- and benzo(a)pyrene-induced CYP1A1 and CYP1A2 mRNAs and EROD activity. Treatment with cycloheximide in combination with 3-MC led to superinduction of CYP1A mRNA, under which conditions TGF-beta 1 did not block induction, suggesting the requirement for protein synthesis for the suppressive effect of the cytokine. In addition, TGF-beta 1 augmented AP-1-binding activity, suggesting that fos and/or jun protooncogene products could be implicated in the response. Our results demonstrate that IL-1 beta, TNF-alpha, and IFNs antagonized PAH-mediated induction of CYP1A gene expression in human hepatocytes. In addition, we report the finding of a novel effect of TGF-beta 1, which was able to prevent CYP1A1 and -1A2 induction by two different PAHs.
Mol Pharmacol 1994 Dec
PMID:Transforming growth factor-beta 1 down-regulates basal and polycyclic aromatic hydrocarbon-induced cytochromes P-450 1A1 and 1A2 in adult human hepatocytes in primary culture. 780 30

In order to evaluate the feasibility of using quantitative polymerase chain reaction (PCR) to evaluate gene dosage, we developed an assay to detect alpha-globin genes, which are frequently deleted in alpha-thalassemia patients. In this quantitative assay alpha-1 and alpha-2 globin consensus regions are coamplified by one oligonucleotide pair, along with a second primer pair targeting a single-copy reference gene, namely, tumor necrosis factor alpha, or TNF-alpha. A series of DNA samples titrating alpha-globin against TNF-alpha DNA have a strong linear relationship between template ratios and product ratios (r > 0.98). Minimal sequence divergence (91% homology) between alpha-1 and alpha-2, internal to the identical primer annealing sites, results in a lower amplification efficiency for alpha-1, to 94% of alpha-2 for each cycle. Furthermore, when applied to a variety of individual DNA samples, the signal ratios of alpha-globin to TNF-alpha were far more variable than previously observed for titrated control DNA. We conclude that DNA isolates from different individuals may have idiosyncratic changes in amplification efficiency owing to polymorphic sequence variation and/or variable presence of unidentified contaminants. Despite these potentially confounding factors, however, we were able to identify by quantitative PCR a single gene deletion later confirmed by Southern blot analysis in 20 individual DNA samples.
Diagn Mol Pathol 1994 Dec
PMID:Evaluation of gene deletions by quantitative polymerase chain reaction. Experience with the alpha-thalassemia model. 786 34

Human alveolar macrophages (AM) produce a number of inflammatory mediators including tumor necrosis factor (TNF). TNF-alpha has been implicated in several forms of lung injury including that associated with oxygen toxicity. To investigate whether oxygen could induce or augment the release of TNF from AM, we acquired AM from nonsmoking volunteers and determined TNF release after in vitro hyperoxia. Although TNF release was not induced by oxygen exposure alone, if lipopolysaccharide (LPS) stimulation occurred simultaneously, there was significant augmentation by 60 and 95% oxygen over LPS-stimulated AM exposed to 21% oxygen. This increase was paralleled by a significant increase of interleukin (IL)-1 beta. Dimethylthiourea (DMTU), a hydroxyl radical scavenger, inhibited this release. The increase in TNF extracellular concentrations induced by hyperoxia was not associated with significant increases in intracellular concentration or detectable mRNA over LPS-stimulated AM exposed to 21% oxygen. We hypothesize that hyperoxia exposure may alter the LPS-stimulated AM cytoplasmic milieu, thus further enhancing TNF-alpha production by a post-transcriptional mechanism.
Am J Respir Cell Mol Biol 1995 Mar
PMID:Hyperoxia amplifies TNF-alpha production in LPS-stimulated human alveolar macrophages. 787 93

Bronchoalveolar lavage (BAL) macrophages from patients with symptomatic or asymptomatic HIV-1 infections were obtained, and their ability to restrict in vitro the growth of an AIDS-associated strain of Mycobacterium avium was compared with cells obtained from normal volunteers. BAL macrophage populations from HIV-1-infected subjects (symptomatic or asymptomatic) spontaneously released significant amounts of IL-6, IL-1 beta, and TNF-alpha, whereas BAL macrophages from normal volunteers released very low amounts of these cytokines. Phagocytosis of M. avium was shown to be similar in both HIV-1-infected subjects and in control subjects. BAL macrophages from HIV-1-infected subjects released significantly greater quantities of IL-6, IL-1 beta, and TNF-alpha than did cells from normal volunteers upon M. avium ingestion. Growth of M. avium was similar in BAL macrophages from all three subject groups. Finally, BAL macrophages from normal volunteers were obtained, and these cells were doubly infected with a macrophage tropic isolate of HIV-1 at a low multiplicity of infection and with an AIDS-associated strain of M. avium. There were no significant differences in cytokine release by cells co-infected with M. avium and HIV-1 and cells infected with M. avium alone. The growth of mycobacteria and the viral replication in doubly infected cells were compared with those in cells infected with only one of the pathogens, and it was shown that HIV-1 infection had no significant effect on M. avium growth.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1994 Oct
PMID:Interaction between Mycobacterium avium and human immunodeficiency virus type 1 (HIV-1) in bronchoalveolar macrophages of normal and HIV-1-infected subjects. 791 17

Treatment of astrocytes with interleukin (IL)-6, -7 and tumor necrosis factor (TNF)-alpha produced a marked increase in the expression of the pS2 gene, an estrogen-inducible gene originally identified in the human breast cancer cell line MCF-7. The effect of IL-6 and TNF-alpha was completely inhibited by the addition of anti-IL-6 monoclonal antibody and anti-TNF-alpha monoclonal antibody, respectively. During the treatment with IL-6 and TNF-alpha, neither increase in thymidine incorporation nor morphological change was observed. Inhibition of protein synthesis by cycloheximide and inhibition of RNA synthesis by actinomycin D abrogated the stimulatory effect on pS2 mRNA expression of IL-6 and TNF-alpha, suggesting that new protein synthesis as well as new RNA synthesis was required for their action. These results suggest that brain injury trigger pS2 gene expression in astrocytes through the induction of cytokines.
Biochem Mol Biol Int 1994 Jun
PMID:Cytokine regulation of PS2 gene expression in mouse astrocytes. 795 Oct 69

Perhaps as many as 25-50% of adult patients and children with acquired immunodeficiency syndrome (AIDS) eventually suffer from neurological manifestations, including dysfunction of cognition, movement, and sensation. How can human immunodeficiency virus type 1 (HIV-1) result in neuronal damage if neurons themselves are for all intents and purposes not infected by the virus? This article reviews a series of experiments leading to a hypothesis that accounts at least in part for the neurotoxicity observed in the brains of AIDS patients. There is growing support for the existence of HIV- or immune-related toxins that lead indirectly to the injury or demise of neurons via a potentially complex web of interactions among macrophages (or microglia), astrocytes, and neurons. HIV-infected monocytoid cells (macrophages, microglia, or monocytes), after interacting with astrocytes, secrete eicosanoids, i.e., arachidonic acid and its metabolites, including platelet-activating factor. Macrophages activated by HIV-1 envelope protein gp120 also appear to release arachidonic acid and its metabolites. In addition, interferon-gamma (IFN-gamma) stimulation of macrophages induces release of the glutamate-like agonist, quinolinate. Furthermore, HIV-infected macrophage production of cytokines, including TNF-alpha and IL1-beta, contributes to astrogliosis. A final common pathway for neuronal susceptibility appears to be operative, similar to that observed in stroke, trauma, epilepsy, neuropathic pain, and several neurodegenerative diseases, possibly including Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This mechanism involves the activation of voltage-dependent Ca2+ channels and N-methyl-D-aspartate (NMDA) receptor-operated channels, and, therefore, offers hope for future pharmacological intervention. This article focuses on clinically tolerated calcium channel antagonists and NMDA antagonists with the potential for trials in humans with AIDS dementia in the near future.
Mol Neurobiol
PMID:HIV-related neuronal injury. Potential therapeutic intervention with calcium channel antagonists and NMDA antagonists. 799 15

Staphylococcus enterotoxins and toxic shock syndrome toxin-1 (TSST-1) are members of the family of staphylococcal exoproteins (SE) which binds specifically to HLA class II molecules and certain V beta T cell receptor phenotypes. These bacterial products have been termed "superantigens" due to their capacity to stimulate a greater proportion of T lymphocytes than peptide antigens without a requirement for antigen processing. The SE stimulate monocytes to secrete IL-1 and TNF-alpha and affect B lymphocyte proliferation in response to anti-human IgM and Ig production by PBMC. The current study concerns the transmission of signals in human B lymphocytes following fixation of TSST-1. Activation of both PLC and PKC are observed while intracellular calcium levels remain unchanged. Levels of HLA class II mRNA were increased suggesting that a pathway leading to activation was triggered. This study therefore identifies some of the second messengers involved after SE fixation on HLA class II molecules and suggests that the signals transmitted via class II antigens as well as those via the TCR may have a role in the physiological responses to bacterial superantigens.
Mol Immunol 1994 Jun
PMID:Bacterial superantigen signaling via HLA class II on human B lymphocytes. 802 2

The presence of cancer induces metabolic alterations in distant, tumor-free tissues and organs of the host. A remote humoral effect of cancer growing extrahepatically is an increase in the activity of oxidant and a decrease of antioxidant enzymes in the liver of the tumor-bearing animal. We speculated that TNF-alpha, produced by host cells, the cancer, or both, is responsible for these changes. When human recombinant TNF-alpha, 100 micrograms/kg/d i.p. for 5 days, was injected in groups of rats fed ad libitum, starved, or pair-fed, a decrease in the activity of superoxide dismutase and glutathione peroxidase and an increase in xanthine oxidase was observed, particularly with pair-fed controls. It is concluded that TNF-alpha, directly or indirectly, causes these enzyme alterations in the tumor-free liver of a tumor-bearing host.
Biochem Mol Biol Int 1994 May
PMID:TNF-alpha effect on oxygen free radical scavenging and generating enzymes in rat liver. 808 Dec 9

Acute lung injury, characterized as the adult respiratory distress syndrome (ARDS), is a common clinical occurrence following blood loss and injury. We previously found increased levels of transforming growth factor (TGF)-beta 1 mRNA in murine intraparenchymal mononuclear cells and in alveolar macrophages within 1 h after hemorrhage. Because TGF-beta has potent proinflammatory and immunoregulatory properties, we investigated the effect of blocking TGF-beta with mAb on hemorrhage-induced pathology, cytokine mRNA levels in lungs, as well as survival from pneumonia. Mice treated with anti-TGF-beta mAb showed normal pulmonary histology 3 days after hemorrhage and resuscitation in contrast to the mononuclear and neutrophil infiltrates, intraalveolar hemorrhage, and interstitial edema found in hemorrhaged mice either treated with control antibody or not treated with any antibody. Decreased mRNA levels for IL-1 beta, TNF-alpha, IL-6, IL-10, and IFN-gamma as compared with untreated, hemorrhaged controls were present in intraparenchymal pulmonary mononuclear cells following therapy with anti-TGF-beta. In contrast, therapy with anti-TGF-beta increased mRNA levels for IL-1 beta and TNF-alpha in alveolar macrophages and for TGF-beta in peripheral blood mononuclear cells collected 3 days after hemorrhage. Administration of anti-TGF-beta to hemorrhaged mice did not correct the enhanced susceptibility to Pseudomonas aeruginosa pneumonia that exists after hemorrhage. These results suggest that TGF-beta has an important role in hemorrhage-induced acute lung injury, but does not contribute to the post-hemorrhage depression in pulmonary antibacterial response.
Am J Respir Cell Mol Biol 1994 Sep
PMID:Anti-transforming growth factor-beta monoclonal antibodies prevent lung injury in hemorrhaged mice. 808 71


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