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)

The effects of phorbol ester (TPA) and other known stimulators such as tumor necrosis factor (TNF), interleukin-1, and lipopolysaccharide on induction of mRNA for manganese-superoxide dismutase (Mn-SOD) were investigated in various cell lines. TPA enhanced Mn-SOD mRNA expression in TNF-resistant cell lines including HeLa cells, in which the other reagents also induced expression of the gene, but did not affect TNF-sensitive cells, in which the other stimulators did not alter expression of the gene. HeLa cells which had been desensitized to TPA by pretreatment with TPA for 24 h expressed Mn-SOD mRNA at a slightly higher level than the cells without TPA treatment. TPA-pretreated cells stimulated with TNF, however, expressed Mn-SOD mRNA at about twice the level of TNF-stimulated, TPA-untreated cells. When protein synthesis was inhibited by cycloheximide during TPA pretreatment, TNF no more enhanced the Mn-SOD mRNA accumulation. These data suggest that at least two separate signal-transducing pathways are involved in expression of this gene. One is triggered by protein kinase C activation itself in the absence of new protein synthesis. The other can be activated by stimulation with TNF, interleukin-1, or lipopolysaccharide and in which a protein factor that can be induced by TPA treatment is involved.
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PMID:Phorbol ester induces manganese-superoxide dismutase in tumor necrosis factor-resistant cells. 174 13

Cytoplasmic pH (pHi) has been shown to be an important determinant of the activity of the NADPH oxidase in phagocytic cells. We hypothesized that a difference in pHi and/or its regulation existed between activated and resident macrophages (RES MOs) which might explain the increased NADPH oxidase activity observed in the former. The pHi of RES and lipopolysaccharide (LPS)-elicited MOs was examined using the fluorescent dye BCECF. Resting pHi did not differ between resident (RES) and elicited (ELI) MOs (7.16 +/- 0.05 and 7.20 +/- 0.05, respectively). pHi recovery after intracellular acid loading was partially dependent on the presence of Na+ in the extracellular medium, and was partially inhibited by the Na+/H+ antiport inhibitor, amiloride. At comparable pHi, the rate of acid extrusion during recovery was not different in RES and ELI MOs (1.48 +/- 0.12 and 1.53 +/- 0.06 mM/min, respectively). In both RES and ELI MOs, approx. 40% of total pHi recovery was insensitive to amiloride and independent of extracellular Na+. In both RES and ELI MOs, stimulation with TPA resulted in a biphasic pHi response: an initial acidification followed by a sustained alkalinization to a new steady-state pHi. This alkalinization was Na(+)-dependent and amiloride-sensitive, consistent with a TPA-induced increase in Na+/H+ antiport activity. The new steady-state pHi attained after TPA stimulation was equivalent in RES and ELI MOs (7.28 +/- 0.04 and 7.31 +/- 0.06, respectively), indicating comparable stimulated Na+/H+ antiport activity. However, the initial acidification induced by TPA was greater in ELI than in RES MOs (0.18 +/- 0.02 vs. 0.06 +/- 0.02 pH unit, respectively, P less than 0.05). The specific NADPH oxidase inhibitor diphenylene iodonium (DPI) completely inhibited the respiratory burst but reduced the magnitude of this pHi reduction by only about 50%. This suggested that the TPA-induced pHi reduction was due in part to acid produced via the respiratory burst, and in part to other acid-generating pathways stimulated by TPA.
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PMID:Regulation of cytoplasmic pH in resident and activated peritoneal macrophages. 215 21

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

A long term cultured cell line (c-WRT-7) was successfully established from the transplantable rat myelomonocytic leukemia (WRT-7). Analysis of cell surface markers and phagocytic properties of c-WRT-7 cell showed that about 10% of c-WRT-7 cells differentiated spontaneously from blastic cells to macrophage-like cells in the culture. The differentiation of c-WRT-7 cells was markedly enhanced by in vitro treatment of cells with lipopolysaccharide (LPS), phorbol ester (TPA) and retinoic acid. Of these chemicals, LPS was the strongest enhancer of the differentiation of c-WRT-7 cells over the wide range of doses tested. The transplantation of c-WRT-7 cells into the peritoneal cavity of WKA rat (derived host) proved lethal with a significant increase of blastic tumor cells. Conversely, in SHR rat, which has a common major histocompatibility antigen with WKA rat (RT-1k), although the transplanted c-WRT-7 cells grew well as was observed in WKA rat, increased blastic cells were replaced by the differentiated macrophage-like cells and finally were rejected. Furthermore, the increasing differentiation activity of c-WRT-7 cells in vitro was detected in the peritoneal fluid and serum of SHR rat accompanied by the transplantation of c-WRT-7 cells. This is significantly different from the case of the Fischer rat with a different major histocompatibility antigen (RT-1l) in which transplanted c-WRT-7 cells scarcely grew and were rejected immediately.
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PMID:[Establishment of rat myelomonocytic leukemia cell line (c-WRT-7)--induction of differentiation and transplantation into syngeneic and non-syngeneic rats]. 260 51

The results of cytogenetic studies are reported in 89 patients with B-cell CLL. LPS (E. coli lipopolysaccharide), PWM (pokeweed mitogen), PHA (phytohaemagglutinin), EBV (Epstein-Barr virus), TPA (phorbol 12-myristate 13-acetate), and LA (leucoagglutinin) were used as mitogens. Mitoses were obtained from 78 cases. Clonal aberrations could be demonstrated in 26 cases. Trisomy 12 was the most frequent finding (8 cases) and was sole abnormality in 4 cases. Chromosomes #14, #17, and #11 were involved in structural aberrations in 5, 7, and 7 cases respectively, but a t(11;14)(q13;q32) was the only structural aberration seen more than once. The median observation time was 47 months (range 1-87). The presence of clonal abnormalities did not influence survival significantly, either when calculated from diagnosis or from cytogenetic analysis. Patients with more than one aberration, however, had a significantly shorter survival than patients with normal mitoses only (p less than 0.05). The survival of 8 patients with trisomy 12 (in 4 as sole abnormality) was not different from that of patients with normal mitoses only.
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PMID:B-cell chronic lymphocytic leukaemia: clonal chromosome abnormalities and prognosis in 89 cases. 261 12

The interaction between human endothelial cells and leukocytes during immunological and inflammatory responses is in part mediated through the release of soluble mediators. We report that cultured human umbilical vein endothelial cells secrete IL-6 when stimulated with lipopolysaccharide. The monokines, IL-1 and TNF-alpha, were potent inducers of IL-6, whereas lymphotoxin was only effective at much higher concentrations. IFN gamma also was a strong stimulus of IL-6 production, but TGF-beta did not have an effect at doses modulating other endothelial cell functions. Endothelial cell IL-6 was active as hybridoma-plasmacytoma growth factor and as B-cell and hepatocyte stimulating factor. Endothelial IL-6 activity was neutralized by a specific antibody to IL-6 and it was shown by immunoprecipitation to be identical in size to human fibroblast-derived IL-6. IL-6 did not have a detectable effect on several endothelial cell functions, including proliferation, adherence of leukocytes, and synthesis of PGE2, TPA, and PAI-1. As IL-6 is probably an important regulator of host defense responses, production of this cytokine by endothelial cells may contribute to the pathogenesis of various inflammatory and immunologic diseases.
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PMID:Human endothelial cells produce IL-6. Lack of responses to exogenous IL-6. 266 Jun 97

Recombinant gamma-interferon (r gamma-IFN) has contrasting effects on thromboplastin (TPL) synthesis induced in monocytes (M) and endothelial cells by bacterial lipopolysaccharide (LPS), phorbol ester (TPA), and phytohaemagglutinin (PHA). In human umbilical vein endothelial cells (HUVEC) the induced thromboplastin response was significantly augmented by r gamma-IFN whereas the monocyte response was inhibited. Recombinant alpha-interferon (r alpha-IFN) had no effect on thromboplastin induction in endothelial cells but had a significant inhibitory effect on the TPL response in monocytes when LPS or LPS and cyclosporin A (CS) were used as inducing agents. Cyclosporin A, previously shown to enhance thromboplastin synthesis induced in monocytes, also contributes to a higher level of thromboplastin activity in endothelial cells. Its effect on monocytes was in most cases fully inhibited by r gamma-IFN (and also by r alpha-IFN when tested). gamma-Interferon and alpha-interferon alone had a weak stimulatory effect or none on thromboplastin synthesis in both cell types.
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PMID:Differential effect of alpha-interferon and gamma-interferon on thromboplastin response in monocytes and endothelial cells. 312 8

We describe clonal chromosome abnormalities in 13 new cases of B-cell type prolymphocytic leukemia (B-PLL) investigated using pokeweed, lipopolysaccharide B, TPA (phorbol ester), and Epstein-Barr virus (EBV) as mitogens. B-PLL showed a much better response to all four mitogens when compared with B-cell chronic lymphocytic leukemia (B-CLL). A 14q+ was the most frequent abnormality and was observed in 7 of the 13 cases. A t(11;14)(q13;q32) was observed in 2 patients in this series and in 2 cases from a previous series of 9 patients studied in this laboratory, giving an incidence in B-PLL of 18% for this abnormality. The more frequent rearrangement of both IgH genes in B-PLL when compared to B-CLL may predispose to a higher incidence of 14q+ in B-PLL. Trisomy 12 which is a feature of B-CLL was observed in one case in the present series. Other abnormalities of chromosome 12 included 12p-(p12-13) in 2 cases and t(12;14)(q22;q32) in 1 case. The t(6;12) previously described as a specific abnormality in B-PLL was not observed in the 22 cases (13 present series, 9 previous series) studied in our laboratory.
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PMID:Cytogenetic studies on prolymphocytic leukemia. 1. B-cell prolymphocytic leukemia. 350 70

In this study we have examined the expression and modulation of the human granulocyte colony-stimulating factor (G-CSF) receptor (R) in immature and differentiated myeloid cells using a 125I labelled human G-CSF analogue (TG50). Equilibrium binding data revealed a single affinity class of receptor on all cell types expressing G-CSFR (KD 235-606 pM) with neutrophils expressing 2883 +/- 672 Rs/cell. Rapid internalization of surface receptor-bound ligand at 37 degrees C was detected in both immature cells (U937) and neutrophils with > 70% of specifically bound ligand internalized within 5 min. Concentration-response data showed that the level of occupancy of neutrophil G-CSFRs by ligand at 37 degrees C was approximately 5-fold greater than predicted by equilibrium binding data and correlated closely with concentration-response data for biological activity. Re-expression of G-CSFRs following down-regulation by internalization was not detected. Down-regulation of the neutrophil G-CSFR by several agents including granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor (TNF), lipopolysaccharide (LPS), f-met-leu-phe (fMLP), phorbol ester (TPA) and C5a was observed at 37 degrees C but not at 4 degrees C. In contrast, G-CSFRs on immature myeloid cells were significantly down-regulated by TPA only. Differentiation of myeloid leukaemic cell line HL-60 with DMSO, a frequently used model of granulocytic differentiation, was associated with a significant reduction in G-CSFR expression (11 +/- 5% of control) whereas treatment with retinoic acid led to increased G-CSFR expression (161 +/- 3%).
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PMID:Expression and dynamic modulation of the human granulocyte colony-stimulating factor receptor in immature and differentiated myeloid cells. 750 64

Superoxide dismutases (SODs) scavenge superoxide anion and participate in an essential role as a defense system against oxidative stress in body. Cu,Zn-SOD is localized at cytoplasm. A defect in the Cu,Zn-SOD gene has been demonstrated in some cases of familial amyotrophic lateral sclerosis. Trisomy of chromosome 21 in Down's syndrome increases the level of this isozyme and causes the disease. Inactivation of Cu,Zn-SOD by glycation under hyperglycemic conditions may also be a critical factor for diabetic complication. The expression of the second isozyme, Mn-SOD localized at mitochondrial matrix, is regulated in a complex manner by many stimulants such as interleukin-1, -6, tumor necrosis factor, lipopolysaccharide, and tumor promoters phorbol ester (TPA) and okadaic acid. This isozyme seems to work as a defense mechanism against damage during inflammatory responses. The third isozyme, extracellular SOD, is highly glycosylated and has affinity for heparin sulfate. This may participate in scavenging superoxide in plasma and, therefore, missense mutation in heparin binding domain increases the serum level of this isozyme, although the physiological role is not clearly understood yet.
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PMID:[Physiological significance of superoxide dismutase isozymes]. 760 83


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