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)

It has been suggested that tumor necrosis factor (TNF) participates in the mechanism of regression of the corpus luteum. We measured luteal expression of TNF alpha mRNA and biological activity during prostaglandin-induced luteolysis in sheep. Initiation of functional luteolysis was marked by a sharp decline in concentrations of progesterone in luteal tissue beginning 4 h after administration of luteolysin. Structural regression of corpora lutea was manifested by a reduction in glandular weight at 16 h. A luteal cytotoxic factor with TNF alpha-like bioactivity was isolated after the decrease in tissue progesterone had occurred, but before evidence of luteal resorption. We were unable to detect temporal alterations in TNF alpha mRNA in luteal samples by classical Northern blot or in situ hybridization analyses. These results imply that luteal TNF alpha is derived primarily as a preformed entity from an extraovarian source, such as infiltrating leukocytes. These results raise the possibility that this cytokine might not be involved in the early stages of luteal regression in the ewe, yet could play a secondary role, perhaps in the subsequent opsonization and removal of degenerating cells.
Mol Cell Endocrinol 1991 Oct
PMID:Analyses of ovine corpora lutea for tumor necrosis factor mRNA and bioactivity during prostaglandin-induced luteolysis. 179 88

Interleukin-1 (IL-1), a cytokine involved in the acute phase reaction to injury and infection, has multiple effects in the central nervous system, including induction of fever and sleep and the release of several neuropeptides. We evaluated effects of IL-1 beta on inhibitory postsynaptic function at the gamma-aminobutyric acidA (GABAA) receptor. IL-1 (100 pg/ml to 10 ng/ml) augmented GABAA receptor function in cortical synaptic preparations. This effect of IL-1 was largely prevented by incubation with a specific IL-1 receptor antagonist. The related cytokines interleukin-6 and tumor necrosis factor did not augment GABA-dependent chloride transport. Similar enhancement of GABAA receptor function was observed in tissue prepared from mice previously injected intraperitoneally with IL-1 (1 microgram). Electrophysiological studies in cultured primary cortical neurons demonstrated that IL-1 enhanced the GABA-mediated increase in chloride permeability, whereas IL-1 alone produced no alterations in resting conductance. Behavioral studies indicated that IL-1 is similarly active in vivo; mice treated with IL-1 showed a decrease in open-field activity and an increase in the threshold for pentylenetetrazol-induced seizures. The interaction of IL-1 with GABAA receptors might account for the somnogenic and motor-depressant effects of this cytokine.
Mol Pharmacol 1991 Feb
PMID:Interleukin-1 augments gamma-aminobutyric acidA receptor function in brain. 184 88

The ability of the central nervous system to produce the cytokine interleukin-1 beta (IL-1 beta) in response to challenge by activators of the mononuclear phagocyte system has been examined in vivo. Unilateral injection of a mixture of gamma-interferon (IFN-gamma) and lipopolysaccharide (LPS) into the forebrain of adult rats induced expression of IL-1 beta mRNA. In situ hybridization of IL-1 beta mRNA showed a gradient of cellular hybridization, which was most intense at the site of IFN-gamma/LPS injection. The reverse transcription--polymerase chain reaction (RT-PCR) was used to demonstrate the presence of IL-1 beta mRNA in normal rat brain, and to confirm increases in IL-1 beta mRNA levels following IFN-gamma/LPS injection. These studies show that IL-1 beta can be induced to high levels within the CNS as a consequence of exposure to potent stimulators of macrophage activation.
Brain Res Mol Brain Res 1991 Jan
PMID:Induction of interleukin-1 beta mRNA in adult rat brain. 185 69

Rat cytokine-induced neutrophil chemoattractant (CINC) is a member of the IL-8 family and its human counterpart is MGSA/gro. Rat neutrophil responses in vitro to rat CINC, human IL-8, and human MGSA/gro were studied. CINC concentrations as low as 1 nM induced apparent chemotaxis of rat neutrophils, but human IL-8 and MGSA/gro required concentrations one or two orders higher than that of CINC to attract neutrophils. These data indicate that human IL-8 and MGSA/gro cannot sufficiently substitute for rat counterparts such as CINC in rats. Therefore, the effect of rat CINC on rats was studied. Intradermally injected 10(-10)-10(-7) M CINC dose-dependently caused infiltration of neutrophils. Significant migration of neutrophils appeared by 30 min, and maximum infiltration was observed around 1-2 hr after the injection. CINC induced quick and transient neutrophil accumulation without lymphocyte and monocyte migration or edema formation. CINC, a member of the IL-8 family but a counterpart of human MGSA/gro-related proteins, is a specific neutrophil chemoattractant and can be distinguished from IL-8, which is a chemotactic factor for lymphocytes and neutrophils.
Exp Mol Pathol 1991 Aug
PMID:Rat CINC, a member of the interleukin-8 family, is a neutrophil-specific chemoattractant in vivo. 188 68

Activated cells of the monocyte-macrophage lineage produce two forms of the inflammatory cytokine interleukin-1 (IL-1), IL-1 alpha and IL-1 beta, of which IL-1 beta is the predominant secreted form and has a wide range of modulatory effects on the endocrine system. Immunoassays of human IL-1 beta have been described, but are not suitable for measurement of rat and mouse IL-1 beta because of limited cross-reactivity. Polyclonal sheep anti-rat or sheep anti-mouse IL-1 beta antisera were used to develop sensitive and specific immunoradiometric assays for rat and mouse IL-1 beta. Secretion of IL-1 beta from endotoxin-activated monocytes or macrophages was measured in vitro or in vivo in both species. In vitro, rat monocytes and mouse macrophages produced IL-1 beta in response to endotoxin, with a relatively small proportion of total IL-1 beta being secreted. In vivo, endotoxin stimulated an increase in plasma IL-1 beta in both animals. The development of these assays will facilitate studies of the role of endogenous IL-1 beta in animal endocrine models.
J Mol Endocrinol 1991 Aug
PMID:Interleukin-1 beta production in vivo and in vitro in rats and mice measured using specific immunoradiometric assays. 189 39

Tumor necrosis factor-alpha (TNF) is a cytokine involved in the pathogenesis of shock and in granuloma formation, tissue necrosis, and fibrosis, in many organ systems, including the lung. It has been suggested that cells from patients infected by the human immunodeficiency virus (HIV + ve) are primed for TNF release. We postulated that TNF release from the alveolar macrophages (AM) of such patients with lung disease might lead to their observed pulmonary dysfunction. We present data confirming that peripheral blood monocytes (PBM) and demonstrating that AM from HIV + ve patients with pulmonary manifestations show significantly greater TNF production than those from HIV-negative (HIV - ve) subjects. In addition, we found sequentially significant increases in TNF production from AM and PBM of HIV + ve patients with no pathogens detected at bronchoscopy (NB), bacterial pneumonia (BP), and those with Pneumocystis carinii pneumonia (PCP). The overall TNF levels were greater from AM than PBM in all groups other than spontaneous production from HIV - ve subjects. Adherent populations of PBM and AM were incubated for 4 h with lipopolysaccharide (10 micrograms/ml) or control medium alone. Cell-free supernatants were examined for the presence of TNF using an immunoassay. The TNF levels (mean +/- SD) in IU/ml from stimulated PBM of the PCP, BP, NB, and control groups, respectively, were 186 +/- 36, 140 +/- 30, 95 +/- 18, and 55 +/- 10 and the spontaneous levels were 123 +/- 25, 100 +/- 22, 75 +/- 24, and 11 +/- 5.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1991 Aug
PMID:Production of tumor necrosis factor-alpha by blood and lung mononuclear phagocytes from patients with human immunodeficiency virus-related lung disease. 189 44

The reservoir of Mycobacterium avium complex (MAC) during human infection is the mononuclear phagocyte. In these studies, the ability of certain macrophage-active cytokines to affect MAC growth in human alveolar macrophages was evaluated. Neither recombinant interferon-gamma (2 x 10(2) to 10(3) U/well of 5 x 10(5) cells) nor recombinant macrophage colony-stimulating factor (20 to 50 ng/well), when tested alone, exhibited a consistent ability to induce macrophage targets to inhibit the growth of a clinical strain of MAC serovar 4. However, the combination of these cytokines (1 to 50 ng macrophage colony-stimulating factor + 10(3) U interferon per well) was remarkably effective in diminishing replication of MAC in all experiments. These cytokines were also able to induce alveolar macrophages to restrict MAC growth even though cells were obtained from several individuals with acquired immunodeficiency syndrome (AIDS) or from normal donors and infected in vitro with the human immunodeficiency virus type 1. The effect of this cytokine combination was not abrogated by 10(4) neutralizing U/ml of anti-tumor necrosis factor-alpha antibody. Rather, the combination of interferon-gamma and macrophage colony-stimulating factor appeared to activate intrinsic macrophage mechanisms for restricting MAC growth and deserves further study to determine the potential value of this cytokine combination in the treatment of human infection.
Am J Respir Cell Mol Biol 1991 Mar
PMID:Growth inhibition of Mycobacterium avium complex in human alveolar macrophages by the combination of recombinant macrophage colony-stimulating factor and interferon-gamma. 190 Apr 25

Interleukin-5 contains only two cysteine residues both of which appear to be involved in the dimerisation of the molecule to form a disulphide-linked homodimer (Minamitake et al., J. Biochem. 107, 292-297, 1990). However, it remains unclear whether this linkage is necessary for the bioactivity of this cytokine. Site-directed mutagenesis was used to produce amino acid substitutions of either or both of the cysteines. The mutant proteins were all biologically inactive monomers, however when the two single mutant constructs were co-transfected, biologically active IL5 was produced. This is consistent with the dimer forming in a head-to-tail configuration.
Mol Immunol
PMID:Mutated interleukin-5 monomers are biologically inactive. 190 78

Leukemia inhibitory factor (LIF) and interleukin-6 (IL-6), two multifunctional cytokines lacking structural homology and binding to distinct receptors, share interesting functional similarities, which include induction of hematopoietic differentiation in normal and myeloid leukemia cells, induction of neuronal cell differentiation, and stimulation of acute-phase protein synthesis in hepatocytes. Structural information on the LIF receptor is not yet available, whereas recent cloning of the IL-6 receptor has shown it to be bipartite, with a signal-transducing subunit that lacks sequence homology to known protein kinases and produces second messengers of unknown nature. The molecular nature of the mechanisms which LIF and IL-6 use to induce cell differentiation is not known. To address this issue, we took advantage of a clone of M1 myeloblastic leukemia cells capable of being induced for terminal differentiation by both LIF and IL-6 directly activate the same set of immediate early response genes upon induction of M1 myeloid differentiation. At least two mechanisms of gene activation, one transcriptional and the other posttranscriptional, are shown to be involved. It is also shown that the LIF and IL-6 immediate early response, at suboptimal cytokine concentrations, is additive. Using a variety of protein kinase activators and inhibitors, we have shown that the intracellular signalling pathways for both LIF and IL-6 are distinct from those of known second messengers and involve protein phosphorylation, notably tyrosine phosphorylation of a 160-kDa protein, as an essential step(s) in the immediate early activation of MyD gene expression. These observations indicate that the functional similarities of LIF and IL-6 as inducers of cell differentiation prevail at the level of the complex differentiation immediate early response and implicate common mechanisms of signal transduction for LIF- and IL-6-induced differentiation.
Mol Cell Biol 1991 Sep
PMID:Leukemia inhibitory factor and interleukin-6 trigger the same immediate early response, including tyrosine phosphorylation, upon induction of myeloid leukemia differentiation. 190 51

Protein phosphorylation is central to multiple regulatory processes in cells. Tumor necrosis factor (TNF), a cytokine synthesized by macrophages, effects polymorphonuclear leukocyte (neutrophil) chemotaxis, induces superoxide anion generation, and mediates neutrophil adhesion to endothelial cells. Although protein phosphorylation is almost certainly involved in many TNF-mediated neutrophil functions, little is known about TNF's impact on neutrophil protein phosphorylation. Therefore, we studied human recombinant TNF-alpha-induced protein phosphorylation in human neutrophils. Neutrophils were preincubated with 32PO(4)2- and treated with a variety of stimulatory agents. One- and two-dimensional polyacrylamide gel electrophoresis was used to analyze phosphorylated proteins. Phosphoaminoacids were identified by two-dimensional thin layer chromatography electrophoresis. The findings were as follows: (1) TNF induces the phosphorylation of two 16-kD proteins (pI = 5.9 and 6.1) by 5- to 6-fold, and a 57-kD protein (pI = 5.8) by 3- to 4-fold compared with untreated neutrophils; (2) these proteins are phosphorylated as early as 15 min after stimulation with TNF, and phosphorylation is induced by concentrations of TNF as low as 1 ng/ml (10 U/ml); (3) TNF induces the phosphorylation of proteins at either serine or threonine residues and not at tyrosine; (4) TNF-stimulated neutrophils show a unique pattern of protein phosphorylation when compared to neutrophils treated with formylmethionylleucylphenylalanine; (5) lipopolysaccharide does not induce protein phosphorylation in neutrophils; (6) a 16-kD protein is phosphorylated in response to TNF in neutrophils but not in mononuclear cells; and (7) protein kinase inhibitors appear to have no effect on TNF-induced protein phosphorylation. Thus, the mechanism of action of TNF on neutrophils may involve protein phosphorylation.
Am J Respir Cell Mol Biol 1991 Sep
PMID:Tumor necrosis factor-induced protein phosphorylation in human neutrophils. 191 Aug 14


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