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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the testis, growth factors and cytokines are synthesized by Sertoli cells and peritubular cells. In different cell types, these mediators are known to regulate the metabolism of extracellular matrix molecules, such as proteoglycans. In this study, we have tested the action of three of these mediators (IL-1 alpha, IL-6 and TGF-beta 1) on the proteoglycan synthesis of rat Sertoli cells. The proteoglycan synthesis was unchanged by IL-1 alpha, nor by IL-6 up to 20 ng/ml, during any maturation stage (14, 21 and 35 days). By contrast, Transforming Growth Factor-beta 1 (TGF-beta 1) enhanced Sertoli cell proteoglycan production from 21 day-old rats, with an optimal response at 1 ng/ml. Kinetic studies showed that the effect of TGF-beta 1 (1ng/ml) was higher after 24 hours of incubation. In presence or in absence of TGF-beta 1, a proteoglycan accumulation was observed in the extracellular compartment between 12 and 48 hours, but this factor did not modify the proteoglycan distribution between cell layer and medium. Furthermore, TGF-beta 1 increased proteoglycan anabolism at all Sertoli cell maturation stages studied but this stimulation was greater for the early maturation stages (14 and 21 days). On the other hand, proteoglycan catabolism was not modified by TGF-beta 1. In conclusion, TGF-beta 1 secreted by rat Sertoli and peritubular cells could modulate, in an autocrine/paracrine way the synthesis of one of the main extracellular matrix components.
Biochem Mol Biol Int 1994 Oct
PMID:Effects of transforming growth factor-beta 1, interleukin-1 alpha and interleukin-6 on rat Sertoli cell proteoglycan synthesis. 783 38

4-Deoxypyridoxine (4-DPD) is a potent antagonist of Vitamin B6 coenzyme which inhibits IL-1, lymphocyte proliferation and has demonstrated that tolerance to skin grafts can be induced by administering splenic cells to pyridoxine-deficient mice. Chronic inflammation induced by dorsal injections of 200 microliters of a 1:40 saturated crystal solution of potassium permanganate (KMnO4) in mice treated or untreated with 4-DPD (400 micrograms/dose), has been investigated. After 7 days all mice developed a subcutaneous granulomatous tissue indicative of a chronic inflammatory response, at the site of injection. KMnO4-treated mice injected intraperitoneally with 4-DPD (400 micrograms/dose) on 5 consecutive days (the first at the same time of induction of the granuloma) show a significant decrease in size and weight of granuloma when compared to mice not treated with 4-DPD (Controls). In addition, in all mice treated with 4-DPD there was a strong inhibition of TNF alpha in serum (P < 0.01) and in supernatant fluids (P < 0.05) from minced granuloma, while IL-6 was inhibited in the supernatant fluids (P < 0.05) of minced granulomas but was not detected in the serum of treated and untreated mice. In this study we show for the first time the antiinflammatory effect of 4-DPD on chronic inflammation and the inhibitory effect of TNF and IL-6 generation in supernatant fluids from minced granulomas.
Mol Cell Biochem 1994 Jul 13
PMID:4-Deoxypyridoxine inhibits chronic granuloma formation induced by potassium permanganate in vivo. 785 32

The reverse transcription polymerase chain reaction (RT-PCR) was used to assess the induction of mRNA of the proinflammatory cytokines IL-1 beta, IL-6 and TNF alpha in the spleen, pituitary, hypothalamus and hippocampus of mice after an intraperitoneal injection of lipopolysaccharide (LPS, 10 micrograms/mouse). The kinetics of cytokine gene expression induced by peripheral LPS in the pituitary and brain structures were different from that observed in the spleen. For IL-1 beta the dose-response curve was also measured and also found to be different. These results support the idea that one pathway by which peripheral immune stimuli affect brain functions includes local synthesis of proinflammatory cytokines in certain brain structures.
Brain Res Mol Brain Res 1994 Nov
PMID:Peripheral administration of lipopolysaccharide induces the expression of cytokine transcripts in the brain and pituitary of mice. 787 46

The conversion of androstenedione to estrone, the reaction mediated by the aromatase enzyme complex, may make an important contribution to the synthesis of estrogens in breast tissues. In the present study, the effect of the cytokine. TNF alpha, on aromatase activity was examined in breast fibroblasts derived from normal and malignant breast tissue. TNF alpha (2.5-10.0 ng/ml), in the presence of stripped fetal calf serum and dexamethasone, significantly stimulated fibroblast aromatase activity in a dose-dependent manner. IL-1 and IL-6 also stimulated fibroblast aromatase activity, but no marked synergism between TNF alpha and IL-1 or IL-6 was detected. Using a specific radioimmunoassay, significant concentrations of TNF alpha were detected in samples of breast cyst fluid and breast tumor cytosol, which had previously been shown to stimulate aromatase activity, but not in conditioned medium from breast tumor-derived fibroblasts. As TNF alpha may be preferentially expressed and produced in the adipose tissue component of the breast, this cytokine may have an important role in regulating estrogen synthesis in normal and malignant breast tissues.
Mol Cell Endocrinol 1994 Dec
PMID:Stimulation of aromatase activity in breast fibroblasts by tumor necrosis factor alpha. 789 4

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

Several functions of alveolar macrophages (AM) are modified by cigarette smoking. AM are the first line of defense in bronchoalveolar spaces and could be depressed in their cytotoxicity to tumor cells in smokers. An assay using A549 cells (human lung adenocarcinoma) as target cells was performed to assess cytostasis mediated by AM and their supernatants (SN) from healthy smokers (n = 8) and nonsmokers (n = 6). Contact-mediated cytostasis was decreased in AM of smokers (n = 8) relative to nonsmokers (n = 6) (22.9 +/- 5.7% versus 42.7 +/- 6.0% [+/- SEM], P < 0.04) and increased after lipopolysaccharide (LPS) stimulation in both groups (34.5 +/- 5.3% versus 46.8 +/- 5.2%, NS). Cytostasis induced by SN from nonstimulated AM was low in both groups and was still lower in smokers after LPS exposure (19.3 +/- 4.5% versus 34.5 +/- 4.8%, P < 0.04). Among cytotoxic factors produced by macrophages, interleukin (IL)-1 beta, IL-6, and tumor necrosis factor alpha (TNF alpha) may play an important role in cytostasis. Recombinant human (rH) IL-1 beta and rHTNF alpha had a moderate cytostatic activity, which was additive, whereas rHIL-6 had no significant activity on A549 cells. Bioactive IL-1 beta, IL-6, and TNF alpha were therefore measured in macrophage SN. Their levels tended to be lower in smokers than in nonsmokers and were much increased after LPS stimulation. Levels of the three cytokines were also found to correlate with each other; furthermore, a good correlation between cytokine levels in SN and cytostasis was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1994 Nov
PMID:Cytostatic activity of alveolar macrophages from smokers and nonsmokers: role of interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha. 794 92

The synthetic antiglucocorticoid RU486 has multiple effects on the immune system. We have recently reported that RU486 suppresses normal lymphocyte proliferation and downregulates interleukin-2 receptors (IL-2R) by decreasing the accumulation of the beta-chain IL-2R mRNA in normal human lymphocytes in culture. To further explore the mechanism of the immunoregulatory actions of RU486, in the present study, we investigated the effects of this molecule on the release of lymphokines from phytohemagglutinin (PHA)-activated normal human peripheral blood lymphocytes (NPBL) in culture. We have found that RU486 differentially regulates the release of lymphokines from PHA-activated NPB lymphocytes. Specifically, RU486 (at concentrations of 1-100 nM) exerts pure antagonist actions by almost completely reversing the inhibitory effects of the glucocorticoid dexamethasone (Dex) on the release of monocyte/macrophages-derived lymphokines, such as IL-1, IL-6, IL-8 and tumor necrosis factor-alpha (TNF-alpha). Dex decreased in a dose-dependent manner the release of the above four lymphokines, with an ID50 of 0.9 +/- 0.1, 4.76 +/- 0.4, 9.8 +/- 1.8, and 1.16 +/- 0.2 nM for IL-1, IL-6, IL-8 and TNF-alpha, respectively. Conversely, RU486 exhibits both agonist and antagonist effects on the release of T-lymphocyte-derived lymphokines. RU486 given alone, exerts agonist/glucocorticoid effects, by decreasing in a dose-dependent manner the release of IL-2 and -3. The maximal inhibitory effect of RU486 was observed at 10 nM and was 64.5 +/- 4.3% of the control value, (n = 6, P < 0.02) for IL-2 and 59.2 +/- 6.3% (n = 6, P < 0.02) for IL-3. The ID50 of RU486 for the release of IL-2 and -3 were 14.6 +/- 2.0 and 11.6 +/- 1.9 nM, respectively, i.e. almost similar with those of Dex. Interestingly, when high doses of RU486 (1 microM) were combined with Dex RU486 exhibited antagonist actions by significantly counteracting the inhibitory effects of Dex on IL-2 and -3 release. In conclusion, the antiglucocorticoid RU486 exhibits complex regulatory actions on lymphokine secretion, dependent upon the type of the lymphokine-producing cell. A pure antagonist effect was observed on the release of monocyte-derived IL-1, IL-6, IL-8 and TNF-alpha. However, when RU486 was given alone it acted as a glucocorticoid agonist on the secretion of T-lymphocyte-derived IL-2 and -3, while combined with the agonist (Dex) it exhibits antagonist effects on the release of the above lymphokines.(ABSTRACT TRUNCATED AT 400 WORDS)
J Steroid Biochem Mol Biol 1994 Oct
PMID:In vitro differential effects of the antiglucocorticoid RU486 on the release of lymphokines from mitogen-activated normal human lymphocytes. 794 52

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

Conformationally constraining selectable peptides onto a suitable scaffold that enables their conformation to be predicted or readily determined by experimental techniques would considerably boost the drug discovery process by reducing the gap between the discovery of a peptide lead and the design of a peptidomimetic with a more desirable pharmacological profile. With this in mind, we designed the minibody, a 61-residue beta-protein aimed at retaining some desirable features of immunoglobulin variable domains, such as tolerance to sequence variability in selected regions of the protein and predictability of the main chain conformation of the same regions, based on the 'canonical structures' model. To test the ability of the minibody scaffold to support functional sites we also designed a metal binding version of the protein by suitably choosing the sequences of its loops. The minibody was produced both by chemical synthesis and expression in E. coli and characterized by size exclusion chromatography, UV CD (circular dichroism) spectroscopy and metal binding activity. All our data supported the model, but a more detailed structural characterization of the molecule was impaired by its low solubility. We were able to overcome this problem both by further mutagenesis of the framework and by addition of a solubilizing motif. The minibody is being used to select constrained human IL-6 peptidic ligands from a library displayed on the surface of the f1 bacteriophage.
J Mol Recognit 1994 Mar
PMID:The making of the minibody: an engineered beta-protein for the display of conformationally constrained peptides. 798 69

Mouse models of infection of the central nervous system (CNS) have been used to study retroviral-induced neurologic disease. Ecotropic-neurotropic murine leukemia virus (MuLV) infection of susceptible neonatal mice causes a neurologic disease characterized by progressive hindlimb paralysis. The lesions consist of chronic noninflammatory spongiform change predominantly involving brainstem and spinal cord. Two molecularly cloned strains of MuLV, ts-1, a temperature-sensitive mutant of Moloney MuLV, and pNE-8, derived from a feral mouse isolate Cas-Br-E, were used in this study. Infected mice were sacrificed at regular intervals postinoculation throughout the time-course of disease. The neuropathology was evaluated using standard histological and immunohistopathological techniques. Tissue concentrations of viral proteins and potentially cytotoxic factors were compared with the histopathology in select regions of the CNS. Areas of extensive vacuolation with neuronal and oligodendroglial infection were observed in spinal cord, brainstem, and cerebellum. High titers of infectious virus were observed within CNS lesions, whereas low titers were observed in morphologically uninvolved areas. Western blot analysis revealed abundant production of viral envelope proteins, which correlated well with infectious virus titers. Serum quinolinic acid (QUIN) concentrations in both groups of noninfected and infected mice were similar. However, CNS tissue concentrations of QUIN, TNF alpha, and IL-6 in ts-1 infected mice were significantly higher than in pNE-8 infected or noninfected mice. The difference in concentration of these factors may be the result of greater activation of macrophages/microglia in ts-1 infected mice. During murine retroviral encephalitis, CNS damage may be mediated by direct infection of CNS cells and may be enhanced by indirect effects of neurotoxic factors possibly secreted by infected/activated macrophages.
Mol Chem Neuropathol 1994 Aug
PMID:Viral load and its relationship to quinolinic acid, TNF alpha, and IL-6 levels in the CNS of retroviral infected mice. 799 24


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