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)

Forty-three dogs and cats with spontaneous tumors were treated with the immunostimulating polysaccharide acemannan by intraperitoneal and intralesional routes of administration. Tumors from 26 of these animals showed histopathological evidence of immunological attack as shown by marked necrosis or lymphocytic infiltration. Thirteen showed moderate to marked tumor necrosis or liquefaction. Twenty-one demonstrated lymphoid infiltration, and seven demonstrated encapsulation. Twelve animals showed obvious clinical improvement as assessed by tumor shrinkage, tumor necrosis, or prolonged survival; these included five of seven animals with fibrosarcomas. It is believed that acemannan exerts its antitumor activity through macrophage activation and the release of tumor necrosis factor, interleukin-1, and interferon.
Mol Biother 1991 Dec
PMID:Efficacy of acemannan in treatment of canine and feline spontaneous neoplasms. 176 73

The relationship between the induction of tumor necrosis factor (TNF) (as an indicator of inflammatory reaction) in tumor tissues and its antitumor effect was investigated in tumor-bearing mice by using nine biologic response modifiers (BRMs) and by exogenous/endogenous TNF therapy following a previously reported protocol. Close correlation between the induction of TNF-rich inflammation in tumor tissues and the antitumor effect of BRM were observed. The results of this study suggest that the conditions necessary for exerting antitumor effects of biologic response modifiers may be the induction of TNF (50 to 200 U/g) at the tumor lesions at an early stage after BRM administration and maintenance of the detectable amount of TNF (approximately 10 U/g) for more than 6 hours. Tumor necrosis factor should also be induced in the liver and spleen so that its activity can be maintained in the tumor lesions.
Mol Biother 1991 Dec
PMID:Intratumoral tumor necrosis factor induction in tumor-bearing mice by exogenous/endogenous tumor necrosis factor therapy as compared with systemic administration of various biologic response modifiers. 176 74

Normal feline bone marrow-derived macrophages released maximum concentrations of interleukin-6, tumor necrosis factor, and interleukin-1 when stimulated with ImuVert (Cell Technology Inc, Boulder, CO, USA) at dosages of 1.0 microgram/ml, 5.0 micrograms/ml, and 10.0 micrograms/ml, respectively. When ImuVert was administered to healthy adult cats, significant elevations in rectal temperature and neutrophil counts were observed 10 and 24 hours after each treatment. Weekly treatment with ImuVert failed to prevent or reverse viremia in cats when initiated prior to or 6 weeks after inoculation with feline leukemia virus.
Mol Biother 1991 Dec
PMID:Evaluation of a biologic response modifier derived from Serratia marcescens: effects on feline macrophages and usefulness for the prevention and treatment of viremia in feline leukemia virus-infected cats. 176 75

We studied the effects of interleukin-1 alpha (IL-1) and tumor necrosis factor-alpha (TNF), alone and in combination, on MCF-7 breast cancer cells to determine whether these cytokines alter cell growth, TNF gene expression, and TNF secretion. We found that IL-1 alone and TNF alone inhibited cell growth in a dose-dependent manner. Each cytokine arrested growth in the G0/G1 phase of the cell cycle, with maximum growth inhibition at 1000 U/ml (P less than 0.05) and 100 U/ml (P less than 0.01), respectively. However, the combination of these two cytokines did not result in greater growth inhibition or a greater percentage of cells arrested in the G0/G1 phase of the cell cycle compared with each cytokine alone. We examined the effect of exogenous IL-1 and TNF on TNF gene expression by Northern blot analysis. In the absence of any cytokine, these cells do not express TNF mRNA. Exposure to IL-1 (1000 U/ml) induced TNF mRNA at 3 h; however, mRNA levels diminished thereafter to barely detectable levels by 24 h. Exposure to TNF (1000 U/ml) also induced TNF mRNA at 3 h, but in contrast to IL-1, the level of enhanced expression persisted at these levels through 72 h of exposure. Secretion of TNF by these cells is induced by exogenous TNF, but not by IL-1. IL-1 and TNF in combination do not produce greater inhibition of growth, greater amounts of TNF mRNA at 3 h, or greater secretion of TNF than that produced by TNF alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1991 Nov
PMID:Interleukin-1 alpha and tumor necrosis factor-alpha (TNF alpha) inhibit growth and induce TNF messenger RNA in MCF-7 human breast cancer cells. 177 75

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

Neonatal rat cortical astrocytes in primary culture synthesize and secrete nerve growth factor (NGF). Interleukin-1 beta(IL-1) and basic fibroblast growth factor (bFGF) treatment of astrocytes increased NGF mRNA content by about 2-fold. The effect of these two factors was specific, because other growth factors, such as tumor necrosis factor-alpha, insulin-like growth factor-1, and epidermal growth factor, failed to change NGF mRNA content. The concentrations of IL-1 and bFGF causing half-maximal stimulation were 1 unit/ml and 1 ng/ml, respectively. The increase in NGF mRNA elicited by IL-1 and bFGF was maximal at 3 hr of incubation. In the presence of IL-1 this increase persisted for 36 hr, whereas in the presence of bFGF the initial increase in NGF mRNA was followed by a decrease to 50% of control levels after 24 hr of incubation. Readdition of bFGF after 24 hr of treatment gave a similar increase in NGF mRNA content, suggesting that the decrease at 24 hr was not due to receptor desensitization. The effect of IL-1 was reversible, because removal of IL-1 after 3 hr of incubation resulted in a decrease of NGF mRNA content to control levels by 6 hr, whereas a readdition of IL-1 at this time led to a 2-3-fold increase in NGF mRNA content after an additional 3 hr of treatment. This second increase in NGF mRNA was also maintained for several hours. The combined treatment of astrocytes with maximally effective doses of IL-1 and bFGF produced an additive increase in NGF mRNA content, suggesting that different mechanisms are operative. Treatment of astrocytes with cycloheximide increased (about 6-fold) NGF mRNA content, and this content failed to increase further with IL-1 or bFGF treatment. Experiments using actinomycin D indicated that IL-1 increased the stability of the NGF mRNA. bFGF treatment failed to change this parameter. Thus, IL-1 increases NGF mRNA content in astrocytes, at least in part, by stabilizing mRNA, whereas bFGF does not affect mRNA stability but may act at the level of NGF gene transcription.
Mol Pharmacol 1991 Aug
PMID:Mechanism of nerve growth factor mRNA regulation by interleukin-1 and basic fibroblast growth factor in primary cultures of rat astrocytes. 187 7

In guinea pigs, inhalation of cotton dust results in an acute pulmonary response with symptoms of increased breathing rate, cough, bronchoconstriction, and periods of apnea. These symptoms resemble those noted in individuals upon exposure to cotton and other organic dusts. A major contaminant of cotton dust is bacterial endotoxin. Because endotoxin, or lipopolysaccharide, is recognized to be a potent stimulator of tumor necrosis factor (TNF), it was postulated that TNF might be released in the lung following cotton dust exposure and associated with the pulmonary inflammatory response. Groups of guinea pigs were exposed to an atmosphere of 33 mg/m3 cotton dust for up to 6 h. At 3, 6, 7.5, and 24 h, lungs were isolated and lavaged to assess cell populations and production of TNF. Neutrophil infiltration was apparent by 3 h as was a marked increase in TNF in bronchial alveolar lavage fluid. Alveolar macrophages (AM) isolated at 3 h showed enhanced release of TNF upon in vitro culture when compared with those isolated at the other time points. AM were found to be primed to release TNF upon ex vivo stimulation with lipopolysaccharide. The greatest effect was noted with AM isolated 1.5 h after the 6-h cotton dust exposure. These results demonstrate the ability of cotton dust to cause release of TNF in the lung and suggest a role for TNF in the inflammatory response to cotton dust.
Am J Respir Cell Mol Biol 1991 Jul
PMID:Release of tumor necrosis factor in guinea pigs upon acute inhalation of cotton dust. 187 56

Hypersensitivity pneumonitis (HP) is an allergic granulomatous interstitial lung disease resulting from a reaction of selected individuals to repeated inhalations of certain antigens. HP is characterized by chronic inflammation, and the development of the disease seems to be immunologically mediated. In farmer's lung, the source of provoking antigen has been found to be actinomycetes such as Micropolyspora faeni. In this study, we show that M. faeni, or antigens thereof, stimulate strong release of proinflammatory cytokines from blood monocytes and alveolar macrophages obtained from nonfarmer volunteers and naive mouse peritoneal macrophages. Interleukin-1 (IL-1) was produced by human alveolar macrophages and murine peritoneal macrophages in response to whole M. faeni and antigens thereof. IL-1 activity was detected in the supernatants at 12 h of incubation and was maximal by 24 to 36 h (200 to 400 U/ml of IL-1). A rabbit antiserum to IL-1 alpha and IL-1 beta neutralized the thymocyte-stimulating activity of the supernatants. Moreover, M. faeni (1 to 100 micrograms of antigen) elicited a strong secretion of tumor necrosis factor-alpha (TNF-alpha) from human alveolar macrophages and monocytes as well as mouse peritoneal macrophages, where 1 micrograms of M. faeni elicited the secretion of approximately 100 U of TNF-alpha from 2 x 10(5) macrophages, and 100 micrograms stimulated the release of approximately 1,000 U of bioactive TNF-alpha. One particle of whole M. faeni per cell was sufficient to induce copious release of TNF-alpha from macrophages or monocytes (100 U of bioactive TNF-alpha; 1,000 pg/ml of antigenic TNF-alpha as seen by radioimmunoassay). Both IL-1 and TNF-alpha productions stimulated by M. faeni were not abrogated by inclusion of polymyxin B. We propose that the direct stimulation of cytokines by M. faeni or antigens thereof may play an important role in HP.
Am J Respir Cell Mol Biol 1991 Aug
PMID:Hypersensitivity pneumonitis: whole Micropolyspora faeni or antigens thereof stimulate the release of proinflammatory cytokines from macrophages. 189 50

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


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