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)

Monokines, including tumor necrosis factor alpha (TNF-alpha), have been implicated in the pathogenesis of several pathologic processes, including atherosclerosis. Because estrogen has been found to offer a certain degree of protection against atherosclerotic progression, we examined the effect of estrogen on the expression of TNF-alpha mRNA in a monocyte-macrophage cell line, THP-1. Cells were exposed to 12-O-tetradecanoylphorbol 13-acetate (TPA, 50 ng/ml) for 48 or 96 h to induce differentiation. Some of the cells were treated with lipopolysaccharide (LPS, 10 micrograms/ml) in the last 3 h and/or ethinyl estradiol (estrogen, 10(-9) M) in the last 20 h. Total cellular RNA was isolated and cDNA synthesized and than coamplified using the polymerase chain reaction (PCR) in the presence of two sets (pairs) of 32P-labeled primers, one for TNF-alpha (product size 325 bp) and the second for the internal control, glyceraldehyde 3-phosphate dehydrogenase (G3PDH; 983 bp). The resultant PCR products were separated by agarose gel electrophoresis, and the ratios of radioactivity incorporated into TNF-alpha PCR products to G3PDH products were used to assess the relative changes in the levels of TNF-alpha mRNA abundance in response to various substances. Treatment with TPA for 48 h induced the expression of TNF-alpha mRNA. Treatment of these TPA-stimulated cells with estrogen caused a 62% decrease in TNF-alpha message abundance (p < 0.01). Similar results were obtained with cells stimulated with TPA for 96 h.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Estrogen modulates the expression of tumor necrosis factor alpha mRNA in phorbol ester-stimulated human monocytic THP-1 cells. 770 11

The purpose of this study is to evaluate the effect of the Escherichia coli lipopolysaccharide on the secretion of phosphatidylcholine, the principal component of pulmonary surfactant, in primary cultures of rat alveolar type II pneumocytes. Lipopolysaccharide stimulated phosphatidylcholine secretion in a time- and dose-dependent manner. At a concentration of 200 micrograms/ml, lipopolysaccharide stimulated the release of phosphatidylcholine 4-fold over the basal secretory rate, and the concentration producing half the maximal response was 20 micrograms/ml. The stimulatory effect of lipopolysaccharide on phosphatidylcholine secretion was additive to that of the protein kinase C activator TPA, which is a potent stimulator of surfactant secretion. Lipopolysaccharide did not activate protein kinase C, which suggests that stimulation of phosphatidylcholine secretion by the endotoxin was through a mechanism independent of protein kinase C activation.
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PMID:Effect of Escherichia coli lipopolysaccharide on surfactant secretion in primary cultures of rat type II pneumocytes. 778 92

The murine macrophage inflammatory protein 1 beta mRNA (MIP-1 beta) is rapidly and transiently induced in macrophages by lipopolysaccharide (LPS), serum or cycloheximide. Functional studies of the MIP-1 beta proximal promoter indicate that it is cell-specific, and serum- and LPS-responsive in macrophages. A 76-bp proximal promoter sequence (-51 to -127 bp) confers cell-specific and LPS-inducible activity when placed upstream from a heterologous promoter in both orientations. One essential cis-regulatory element within the enhancer-like sequence is an activating transcription factor/cAMP response element (CRE)-binding protein (ATF/CREB)-binding site, although the promoter is not cAMP responsive. Electrophoretic mobility shift assays and mutational analyses suggest that the promoter site is bound by nuclear protein complexes containing cAMP-independent members of the ATF/CREB family of proteins and c-Jun, and are functionally distinct from the AP1-related TPA-response element (TRE) binding activity.
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PMID:An ATF/CREB-binding site is essential for cell-specific and inducible transcription of the murine MIP-1 beta cytokine gene. 783 96

Human peritoneal macrophages were collected from dialysis bags of renal patients on Continuous Ambulatory Peritoneal Dialysis (CAPD), during an inflammation-free period. The macrophage suspension was cultured in presence of bacterial lipopolysaccharide (LPS) and phorbol myristate acetate (TPA). The cultured macrophages were tested for therapeutic effectiveness against a human tumor-cell line, RC43, implanted subcutaneously in NMRI nude mice. The macrophages were injected around the tumor starting from the 14th day after inoculation, when the tumor growth was already detectable (mean tumor size 7 mm). Three injections of macrophages on days 14, 18 and 21 induced hemorrhagic patches at the tumor site and almost complete regression of the tumor. One injection of macrophages cultured either in presence of LPS+TPA or of LPS+TPA+PGE2 resulted in marked slow-down of the tumor growth. Injection of either TNF-alpha (4000 U/mouse) or PGE2 (150 ng/mouse) given at the site of the palpable small tumor had no effect. Macrophages cultured in medium or in medium supplied with either TPA, LPS or TPA+LPS, were not effective in nude mice bearing large (16 to 19 mm) tumors. The results obtained suggest that activated human macrophages might be therapeutically effective at certain stages of human cancer.
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PMID:Therapeutical effect of activated human macrophages on a human tumor line growing in nude mice. 792 26

The human Mono Mac 6 cell line exhibits many characteristics of mature blood monocytes including expression of the CD14 molecule and production of cytokines, such as interleukin-1 (IL-1), IL-6, and tumor necrosis factor. To determine whether these cells can be further differentiated, we treated the cells for up to 3 days with either prostaglandin E2 (PGE2; 10(-5) or 10(-6) M), lipopolysaccharide (LPS; 10-20 ng/ml), or tetradecanoylphorbol-13-acetate (TPA; 10-50 ng/ml). All three reagents reduced proliferation and expression of the early myelomonocytic antigen CD33, and all increased phagocytosis of staphylococci and constitutive expression of mRNA for the macrophage colony-stimulating factor (M-CSF) receptor. By contrast, with respect to CD23 (Fc epsilon RII) expression, CD14 expression, and production of O2-, the three reagents induced distinct responses. Expression of CD23 (Fc epsilon RII) on Mono Mac 6 cells (36%) was not increased by LPS and TPA but was increased by PGE2 treatment to 48%, with a 50% increase of fluorescence intensity. The CD14 antibody My4 stained more than 75% of untreated Mono Mac 6 cells with a specific mean fluorescence intensity of 87.5 channels. This staining was increased more than twofold by both PGE2 and LPS. Staining with the CD14 antibody UCHM1 (6%) was increased to 43% by PGE2 and to 43% by LPS. This increase in CD14 cell surface expression was accompanied by a rise in soluble CD14 and enhancement of CD14 mRNA. By contrast, TPA treatment resulted in a twofold decrease of CD14 cell surface staining with no significant change in sCD14, while CD14 mRNA was transiently down-regulated. Secretion of O2- (stimulated by TPA) was already detectable in untreated Mono Mac 6 cells (6.1 mmol/10(6) cells/30 min), and this response was enhanced 10-fold by pretreatment with LPS but not with PGE2 or TPA. The kinetics of M-CSF receptor mRNA, CD14 expression, and O2- production revealed that these monocytic features started to increase at 6-24 h and were maximal at 2 days. These data suggest that the three reagents induce maturation of the Mono Mac 6 cells to different levels or into different branches of the monocyte system with the notable differences that PGE2 enhances CD23 expression, LPS enhances O2- secretion, and TPA down-regulates CD14.
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PMID:Distinct patterns of differentiation induced in the monocytic cell line Mono Mac 6. 828 42

Murine peritoneal exudate macrophages (PEM) co-express granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage CSF (M-CSF) receptors, among others. Treatment of PEM with lipopolysaccharide (LPS) or tumor-promoting phorbol ester (12-O-tetradecanoylphorbol-13-acetate [TPA]) induces a rapid but transient loss of M-CSF receptors in PEM. GM-CSF receptors are not affected by this treatment. The loss of M-CSF receptors induced by LPS can be inhibited by neomycin and compound 48/80, two potent phospholipase C (PLC) inhibitors, but not by phospholipase A2, calpain, protein kinase C (PKC) or protease inhibitors. On the other hand, the loss of M-CSF receptors induced by TPA has been prevented by PKC inhibitors but not by PLC inhibitors. PLC inhibitors also prevent LPS-suppressed receptor-mediated internalization of radiolabeled recombinant human (rh) M-CSF by macrophages. Similar prevention of LPS-induced M-CSF receptor downregulation was observed in human monocytes that had been pretreated with PLC inhibitors. Our results show that 1) TPA-induced M-CSF receptor loss is strictly dependent on PKC activation; 2) PLC activation alone also leads to downregulation of M-CSF receptors; and 3) LPS-induced M-CSF receptor downregulation in PEM is mediated primarily through a PLC-dependent pathway. Our data also imply that the expression of M-CSF but not GM-CSF receptors is linked to an important, yet unknown, PLC-sensitive component(s) whose hydrolysis may lead to downregulation of M-CSF receptors.
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PMID:Downregulation of M-CSF receptors by lipopolysaccharide in murine peritoneal exudate macrophages is mediated through a phospholipase C dependent pathway. 851 62

A panel of two poorly differentiated (HA22T/VGH and SK-Hep-1) and six well-differentiated (HuH-6-cl 5, HuH-7, PLC/PRF/5, Hep G2, Hep 3B, and Tong) human hepatocellular carcinoma (HCC) cell lines were studied for the production of colony-stimulating factors (CSFs) using the granulocyte and macrophage colony formation (CFU-GM) assay, immunocytochemical staining, and Northern blotting. Medium conditioned by untreated HA22T/VGH cells contained a high level of CSFs that could stimulate the in vitro colony formation of human myeloid progenitor cells. The HA22T/VGH cell-derived CSF had an apparent molecular weight of 23 kD. Its activity could be effectively neutralized by antiserum against granulocyte-macrophage CSF (GM-CSF) but not by antibodies to other hematopoietic growth factors, including G-CSF, M-CSF, interleukin-3 (IL-3), and IL-6. Correspondingly, immunocytochemical studies using monoclonal anti-GM-CSF showed a strong positive reaction in the cytoplasm of the HA22T/VGH cells. Northern blot analysis revealed that untreated HA22T/VGH cells expressed a considerable amount of GM-CSF mRNA, confirming that GM-CSF production was constitutive. At optimal concentrations, lipopolysaccharide (LPS), IL-1beta, interferon-gamma (IFN-gamma), and tumor-promoting phorbol diester (TPA) could all stimulate HA22T/VGH cells to secrete GM-CSF. In addition to HA22T/VGH, SK-Hep-1 cells could also produce GM-CSF, although less effectively, whereas all the well-differentiated HCC cell lines tested were negative for CSF production. Morphologic, cytochemical, and immunocytochemical examinations demonstrated that both poorly differentiated CSF-producing HCC cell lines (HA22T/VGH and SK-Hep-1) were macrophage-like in morphology, possessed nonspecific esterase (NSE) activity, and expressed CD14, CD68, and HLA-DR on their surface, while all the well-differentiated HCC cell lines were epithelioid and lacked myeloid differentiation antigens. These results suggest that monocytoid features and CSF production may be differentiation markers of hepatocytes at the immature stages, amd that the HA22T/VGH and SK-Hep-1 cell lines may be valuable tools for the study of hepatic function and differentiation.
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PMID:Constitutive production of colony-stimulating factors by human hepatoma cell lines: possible correlation with cell differentiation. 859 73

Activation of glial cells and the consequent release of cytokines, proteins, and other intercellular signaling molecules is a well-recognized phenomenon in brain injury and neurodegenerative disease. We and others have previously described an inducible prostaglandin G/H synthase, known as PGHS-2 or cyclooxygenase-2, that is up-regulated in many cell systems by cytokines and growth factors and down-regulated by glucocorticoid hormones. In cultured mouse astrocytes we observed increased production of prostaglandin E2 (PGE2) after stimulation with either interleukin-1 beta (IL-1 beta) or the protein kinase C activator phorbol 12-myristate 13-acetate (TPA). This increase in PGE2 content was blocked by pretreatment with dexamethasone and correlated with increases in cyclooxygenase activity measured at 4 h. Northern blots revealed concomitant increases in PGHS-2 mRNA levels that peaked at 2 h and were dependent on the dosage of IL-1 beta. Dexamethasone inhibited this induction of PGHS-2 mRNA by IL-1 beta. TPA, basic fibroblast growth factor, and the proinflammatory factors tumor necrosis factor alpha and lipopolysaccharide, but not interleukin-6, also stimulated PGHS-2 mRNA expression. Relative to IL-1 beta, the greater increases in PGE2 production and cyclooxygenase activity caused by TPA correlated with a greater induction of PGHS-2 mRNA. Furthermore NS-398, a specific inhibitor of cyclooxygenase-2, blocked > 80% of the cyclooxygenase activity in TPA-treated astrocytes. These findings indicate that increased expression of PGHS-2 contributes to prostaglandin production in cultured astrocytes exposed to cytokines and other factors.
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PMID:Interleukin-1 beta induces prostaglandin G/H synthase-2 (cyclooxygenase-2) in primary murine astrocyte cultures. 863 79

Astrocytes play an important role in initiating and modulating inflammatory responses within the central nervous system. Extensive studies in rodents have shown that TPA, substance P, calcium ionophore A21387, and lipopolysaccharide (LPS) induce formation and release of arachidonic acid metabolites which have immunoregulatory properties. To better understand the immunopathology of brain injury, we studied the role of inflammatory cytokines such as tumor necrosis factor alpha, interleukin (IL) 6, IL-2, interferon gamma and IL-1 beta in the production of arachidonic acid metabolites in cells from fetal human brain. Among these cytokines, only IL-1 beta significantly stimulated production of prostaglandins E2 and F2 alpha but not PGD2, thromboxane B2 and 6-keto-PGF1 alpha. Under our experimental conditions, these astrocyte cultures did not produce metabolites in the lipoxygenase pathway such as leukotrienes B4 and C4 upon IL-1 beta stimulation. The stimulatory effects of IL-1 beta on the induction of arachidonic acid metabolites have been studied in various human cell types but not in astrocytes. Human astrocyte production of PGF2 alpha and PGE2 but not PGD2, 6-keto-PGF1 alpha and TXB2 when stimulated by IL-1 beta, is thus a novel finding. This observation should initiate investigations into the mechanism of arachidonic acid metabolism and the role of its metabolites in inflammation in the human nervous system.
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PMID:Recombinant human interleukin 1 beta induces production of prostaglandins in primary human fetal astrocytes and immortalized human fetal astrocyte cultures. 898 97

The results of cytogenetic studies are reported in 76 patients with B-chronic lymphoproliferative disorders (B-CLPD): 60 patients with chronic lymphocytic leukemia (CLL), six with follicular lymphoma in leukemic phase (FLLP), five with splenic B-cell lymphoma with villous lymphocytes (SLVL), two with chronic prolymphocytic leukemia (CPL), two with hairy cell leukemia (HCL), and one with plasma cell leukemia (PCL). PHA (phytohemagglutinin), PWM (pokeweed mitogen), LPS (lipopolysaccharide from Escherichia Coli), TPA (phorbol 12-myristate acetate), IL6 (interleukin 6), and DxS (dextran sulfate) were used as mitogens. Mitoses were obtained in 75 cases. Clonal aberrations could be demonstrated in 34 cases (44%). In CLL, classical type, chromosomes 6, 11, and 13 were more frequently involved, whereas trisomy 12 was frequently found in CLL mixed-cell type, in FLLP, and CPL. In SLVL the deletion del(7)(q32) is noteworthy and miscellaneous chromosome abnormalities in the remaining patients were observed. Regarding the efficiency of mitogens, PHA turned to be the most effective in obtaining metaphases and in detecting clonal chromosomal aberrations.
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PMID:Cytogenetic studies in seventy-six cases of B-chronic lymphoproliferative disorders. 907 2


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