Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasminogen activator inhibitor 2 (PAI-2) plays an essential role in the regulation of localized extracellular proteolysis by its inactivation of urokinase. Using probes derived from a cDNA we isolated from lipopolysaccharide (LPS)-stimulated human peripheral blood monocytes, we have mapped, isolated, and determined the molecular organization of the gene for PAI-2 (PLANH2). In situ hybridization of the cDNA to normal metaphase chromosomes has confirmed our prior assignment of the gene for PAI-2 to chromosome 18 and further localized it to the long arm at 18q21.2-18q22. We have isolated nine independent genomic clones, two of which were found to contain the entire PAI-2 transcriptional unit of approximately 16.4 kilobase pairs (kbp). Analysis of the gene organization by restriction enzyme mapping, Southern blotting, and DNA sequencing revealed that the cDNA sequence is divided among eight exons interrupted by seven introns, the junctions of which all conform to the "GT-AG" consensus rule. In common with the arrangement found throughout, the serpin superfamily, of which PAI-2 is a member, the first intron is located just 5' to the initiator methionine residue, and the 3' untranslated region (UTR) is not interrupted by a splice junction. Determination of the transcription initiation site by primer extension analysis of monocytic mRNA indicated that our PAI-2 cDNA was, at most, only three nucleotides short of full length, yielding a primary PAI-2 transcript with a 66-bp first exon. A promoter "TATAAAbox" is located 30 bp upstream of the "cap" site.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chromosomal organization and localization of the human urokinase inhibitor gene: perfect structural conservation with ovalbumin. 230 56

During inflammation a number of liver-derived plasma proteins increases in concentration. In the rat these so-called acute-phase proteins are mainly proteinase inhibitors, such as alpha 1-proteinase inhibitor, alpha 1-acute-phase globulin and alpha 2-macroglobulin. At present, the mechanisms responsible for the enhanced synthesis of acute-phase proteins are poorly understood. Therefore, we have studied the induction of alpha 2-macroglobulin synthesis in rat hepatocyte primary cultures. Adrenaline, triiodothyronine, estradiol and progesterone were tested for their ability to stimulate alpha 2-macroglobulin synthesis. Only triiodothyronine induced alpha 2-macroglobulin synthesis markedly. However, the presence of dexamethasone was a prerequisite for alpha 2-macroglobulin induction indicating a permissive action of glucocorticoids. Besides glucocorticoids and triiodothyronine a non-dialyzable factor (HSF) derived from rat Kupffer cells or human peripheral blood monocytes was found to be able to stimulate alpha 2-macroglobulin synthesis in hepatocytes. Equal amounts of HSF activity were found in conditioned media from lipopolysaccharide-stimulated and unstimulated rat Kupffer cells as well as in human monocytes. Since the supernatants of unstimulated rat Kupffer cells or human monocytes did not exhibit interleukin 1 activity, HSF activity distinct from interleukin 1 must exist. No HSF activity was found in media conditioned by rat Kupffer cells which had been treated with dexamethasone. Hepatocyte primary cultures were incubated with [35S]methionine-labeled proteins secreted by rat Kupffer cells. A 30 kDa polypeptide was found to be bound to or internalized by rat hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The acute-phase induction of alpha 2-macroglobulin in rat hepatocyte primary cultures: action of a hepatocyte-stimulating factor, triiodothyronine and dexamethasone. 242 35

We examined the effect of maleyl-BSA on specific protein expression in murine peritoneal macrophages by radiolabeling treated macrophages with [35S]methionine followed by SDS-polyacrylamide gel electrophoresis. Such treatment induces the expression of a set of at least seven proteins (38, 42, 57, 65, 75, 80, and 85 kD). A similar set of proteins is also induced by treatment of macrophages with the algal polysaccharide fucoidan. The proteins resemble those induced in response to treatment of this same cell population with bacterial lipopolysaccharide (LPS), as judged by co-migration in both one- and two-dimensional electrophoresis. Two proteins induced by either LPS or maleyl-BSA (e.g., p57 and p85) show similar primary structure, as assessed by partial proteolytic peptide mapping confirming their identity. The induction of these proteins by maleyl-BSA is a transient phenomenon, being expressed as early as 1 hr after treatment and declining after 8 hr even in the continuous presence of the stimulus. The dose of maleyl-BSA required to induce the response varies to some extent with the protein in question, but agrees with the Kd for ligand-receptor binding. Chloroquine, which blocks the degradation of ligand, does not inhibit the induction of early protein synthesis. Whereas the induction of these proteins is blocked by inhibition of RNA synthesis with actinomycin D, the reversible inhibition of protein synthesis with cycloheximide during the induction phase does not prevent their expression. LPS, maleyl-BSA, and fucoidan previously have been shown to stimulate protease secretion and tumoricidal function in appropriately primed macrophages. The present findings now demonstrate that all three agents can also mediate the expression of early genes which may participate in the acquisition of functional competence.
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PMID:Maleyl-BSA and fucoidan induce expression of a set of early proteins in murine mononuclear phagocytes. 243 50

Experiments were conducted to determine the influence of immunologic stress on methionine and lysine requirements of growing chicks. Immunologic stress was elicited by injection of either Escherichia coli lipopolysaccharide or heat-killed Staphylococcus aureus every other day for 6 d. In the first experiment, diets were formulated to provide methionine levels of 0.30, 0.50 and 0.70%. In the second experiment, diets contained 0.75, 0.90 or 1.2% lysine. In chicks fed amino acid-sufficient diets, those chicks injected with immunogens had slower growth, lower feed intake and poorer efficiency of feed utilization than those injected with saline. The decreases due to immunogens were diminished in chicks fed amino acid-deficient diets. The methionine requirements of saline- and immunogen-injected chicks were above 0.5% and between 0.3 and 0.5%, respectively; the lysine requirements were greater than 0.95% and between 0.7 and 0.95%, respectively. Thus immunogen injection decreased methionine and lysine requirements, probably because of a decreased need of amino acids for growth and tissue accretion. Immunogen-induced depression in serum zinc and increase in serum copper levels were ameliorated by lysine or methionine deficiencies. Compared with saline-injected chicks, immunogen-injected chicks had significantly higher serum interleukin-1 (IL-1) activity by 53% when fed the methionine-sufficient diet, but they did not have significantly greater IL-1 levels when fed the methionine-deficient diet. These observations indicate that the diminished expression of immunologic stress in amino acid-deficient chicks is due to an impaired immune response.
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PMID:Decreased amino acid requirements of growing chicks due to immunologic stress. 245 41

Phorbol esters induce the differentiation of the human promonocytic cell line U937 to a monocyte/macrophage. This process is associated with the induction of interleukin 1 beta (IL-1 beta) gene expression (Strulovici, B., Daniel-Issakani, S., Oto, E., Nestor, J., Jr., Chan, H., and Ping-Tsou, A. (1989) Biochemistry 28, 3569-3576). Here we describe the induction by phorbol esters of lipopolysaccharide (LPS) responsiveness in U937 cells. Preincubation with phorbol myristate acetate (TPA, 5 x 10(-8) M) for at least 4-6 h and up to 12 h followed by 3 h of LPS treatment induced a 4-fold enhancement in the accumulation of IL-1 beta transcripts compared to treatment with TPA alone. This "priming" effect was specific for protein kinase C agonists and required de novo protein synthesis. Exposure of [35S]methionine-labeled U937 cells to phorbol esters induced the de novo synthesis of a protein which migrated with a 40-kDa molecular mass in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, had an isoelectric point of 5.7 (p 40/5.7), and was recognized by a specific antibody to the pertussis toxin (PT)-sensitive Gi2. The time course for the appearance of Gi2 correlated with that for the induction of LPS responsiveness by TPA. Moreover, the LPS response was PT-sensitive. In cells treated with LPS for 5 min, Gi2 showed diminished ADP-ribosylation by PT. Treatment of U937 cells with LPS for 30 min induced phosphorylation of Gi2 and enhanced PT labeling. In a cell-free assay, phosphorylation of Gi2 by protein kinase C type III, rendered it a better PT substrate. The present findings thus suggest: 1) that TPA induces LPS responsiveness in U937 cells via de novo synthesis of Gi2; 2) that the LPS response (enhanced IL-1 production) is linked to a pertussis toxin-sensitive G protein which we identified as Gi2; and 3) that LPS leads to phosphorylation of Gi2.
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PMID:Lipopolysaccharide response is linked to the GTP binding protein, Gi2, in the promonocytic cell line U937. 251 Dec

The effects of methionine-enkephalin (Met-Enk) on mitogenic and mixed lymphocyte culture (MLC) proliferation of splenocytes from Zn-deficient, restricted and control mice were evaluated. The data from this experiment show that Met-Enk can suppress the responses of splenocyte from the 3 groups to concanavalin A (Con A), but less inhibition was observed in the Zn-deficient group. Met-Enk can also enhance the responses to pokeweed mitogen (PWM) and decrease the response to lipopolysaccharide (LPS) in all groups. Alteration of proliferative responses to Con A and PWM were reversible in the presence of naloxone 10 mumol/L indicating that the effect of Met-Enk on cellular proliferation was mediated by the opioid receptor. In the proliferation of MLC, the response of lymphocytes from Zn-deficient mice was increased in the absence of Met-Enk and Met-Enk can suppress this increased response. It is therefore concluded that Met-Enk can modify the pattern of mitogenic responses and the alteration in Con A and MLC responses can be influenced by zinc deficiency.
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PMID:Methionine-enkephalin alteration of mitogenic and mixed lymphocyte culture responses in zinc-deficient mice. 253 55

Plasma endotoxin concentrations and oxidative burst response of peripheral blood polymorphonuclear leukocytes were examined in 12 patients undergoing coronary artery bypass. The measurements were made just before the operation, 5 minutes after removal of the aortic crossclamp, and 24 hours after the operation. Endotoxin was quantitated by a combination of a sensitive Limulus amebocyte lysate assay and rocket immunoelectrophoresis measuring picogram amounts of endotoxin. Peripheral blood neutrophils were purified by a two-step dextran sedimentation and metrizoate sodium Ficoll (Lymphoprep., Nyegaard, Oslo, Norway) centrifugation. The oxidative burst response of these cells was measured for their ability to generate superoxide anion and was determined by a cytochrome c reduction assay. Preoperatively, all the plasma samples except one were free of endotoxin. The endotoxin levels reached 100 pg/ml 5 minutes after removal of the aortic crossclamp, and except in one sample they had decreased 24 hours after the operation. Studies on the generation of superoxide by neutrophils showed a decline in the response 5 minutes after removal of the aortic crossclamp and an enhancement of the response to f-Met-Leu-Phe by cells obtained from 11 of 12 patients 24 hours postoperatively. In vitro addition of bacterial lipopolysaccharide to blood from healthy individuals also enhanced the superoxide response of the neutrophils. We conclude that during cardiopulmonary bypass the circulating blood is contaminated by endotoxin and the neutrophils are primed for enhanced generation of oxygen radicals. The released oxygen radicals may be involved in the tissue damage observed in these patients.
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PMID:Endotoxemia and enhanced generation of oxygen radicals by neutrophils from patients undergoing cardiopulmonary bypass. 254 7

Recent evidence has implicated enkephalins as immunomodulators. Several studies have reported the regulation of tumor growth by methionine enkephalin (ME). However, there has been little effort to relate the immunological significance of enkephalins to the development of anticancer drugs. The present study had three aims: first, to compare the antitumor activity of the synthetic peptide, D-[Ala2]methionine enkephalinamide (MEA), with endogenous enkephalins on PYB6 fibrosarcoma tumor growth; second, to determine whether tumor growth inhibition was mediated by an opiate receptor; and third, to investigate the effects of MEA on selected immune responses. Female B6C3F1 mice were injected i.p. daily for 7 days with 50-4000 micrograms/kg of ME, MEA, leucine enkephalin (LE) or D-[Ala2]leucine enkephalinamide (LEA), beginning 1 day after PYB6 inoculation. ME and MEA, but not LE or LEA, decreased the PYB6 growth rate. The dose of 50 micrograms/kg MEA exerted the maximum inhibition of tumor growth (nearly 72% on day 15 post tumor transplantation). MEA was not directly toxic to PYB6 tumor cells, as evaluated by the measurement of DNA synthesis and cellular ATP levels of PYB6 cells exposed to MEA in vitro. No [3H]-etorphine specific bindings were detected on the cell membrane or sonicates of splenic lymphocytes or PYB6 cells. Therefore, the antitumor activity by MEA is likely mediated by an indirect mechanism. Immunological studies indicated that MEA selectively enhanced the lymphoproliferative response to the T-cell mitogen, concanavalin A, but not to the B-cell mitogen, lipopolysaccharide.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antitumor activity of enkephalin analogues in inhibiting PYB6 tumor growth in mice and immunological effects of methionine enkephalinamide. 255 21

Methionine-enkephalin, an endogenous opioid, has been reported to have some effects on immune responses. By thymocyte proliferation method, we herein report that methionine-enkephalin over a wide range of concentrations (1 pmol-0.1 mumol/L) significantly increases both extracellular interleukin-1 release and intracellular interleukin-1 production from peritoneal macrophages induced by lipopolysaccharide in mice. Naloxone, having no effect per se on interleukin-1 production, does not block the enhancing effect of the neuropeptide. Interleukin-1 production was also elevated following ip methionine-enkephalin into mice. The results suggest that methionine-enkephalin mediates the enhancement of interleukin-1 synthesis and release as well, and that the effect is not mediated through classical opioid receptors. The results also provide the further links between immune and nervous systems.
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PMID:Enhancement of interleukin-1 production in mouse peritoneal macrophages by methionine-enkephalin. 261

Two highly phosphorylated vimentin-like proteins, pp58 and pp60, are expressed in macrophages activated in vivo to tumouricidal activity. Resident and elicited, non-tumouricidal peritoneal macrophages displayed low and intermediate levels of phosphorylated pp58 and pp60, respectively. C3H/HeN macrophages became tumouricidal after incubation with 0.1 micrograms/mL A23187 plus 10 nmol/L 12-phorbol 13-myristate acetate (PMA), or 0.1 micrograms/mL A23187 plus 100 ng/mL lipopolysaccharide (LPS), and displayed increased phosphorylation of pp58 and pp60. LPS non-responder C3H/HeJ macrophages were not tumouricidal nor did they show increased phosphorylation of pp58 and pp60 after incubation with LPS plus A23187 in vitro. C3H/HeJ macrophages, however, did become tumouricidal and expressed increased phosphorylation of pp58 and pp60 after incubation with A23187 and PMA. Addition of PGE2 (10(-8) mol/L), resulted in down-regulation of macrophage tumouricidal activity and decreased pp58 and pp60 phosphorylation, which was reversed by addition of indomethacin (10(-6) mol/L) to cultures with PGE2. Phosphorylation increased within 5 min after adding activating stimuli while incorporation of [35S]-methionine into a 58 kD protein did not occur until 6 h later. No 60 kD protein synthesis was detected during the first 8 h after adding activating stimuli, indicating that previously synthesized proteins were phosphorylated during macrophage activation. These results signify a physiological role for the phosphorylation of cytoskeleton-associated pp58 and pp60 during macrophage activation to tumour cytotoxicity.
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PMID:Phosphorylation of cytoskeleton-associated proteins, pp58 and pp60, in tumouricidal murine peritoneal macrophages. 261 79


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