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)

In murine macrophages, the anti-tumor agent, paclitaxel, induces expression of a wide variety of inflammatory and anti-inflammatory genes, and causes cytokine secretion via signaling pathways that overlap with those engaged by lipopolysaccharide (LPS), the endotoxic component of Gram-negative bacteria. Using semi-quantitative RT-PCR for detection of gene expression, coupled with ELISA for the detection of secreted gene products, we analyzed the responsiveness of an extensive panel of cytokine and non-cytokine genes to induction by paclitaxel and LPS in the murine DA-3 breast cancer line. A subset of the genes examined (e.g., G-CSF, MIP-2, iNOS, and IL-1 beta, and GM-CSF) was upregulated >3-20-fold by both LPS and paclitaxel in the DA-3 cell line, while IP-10 mRNA was induced by paclitaxel, but not by LPS. In the human MDA-MB-231 breast cancer cell line, LPS also increased mRNA levels for both GM-CSF and IP-10 significantly, while, paclitaxel increased IP-10 mRNA levels with delayed kinetics and failed to induce GM-CSF mRNA. Co-cultures of murine breast cancer cells and macrophages, stimulated with IFN-gamma plus either paclitaxel or LPS, resulted in augmented release of nitric oxide. As both GM-CSF and IP-10 have been implicated in tumor rejection in vivo through either indirect actions on the host immune system or by inhibiting tumor angiogenesis, our data strengthen the hypothesis that tumor cell-derived inflammatory mediators may, in part, underlie the anti-tumor efficacy of paclitaxel in breast cancer.
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PMID:Induction of proinflammatory and chemokine genes by lipopolysaccharide and paclitaxel (Taxol) in murine and human breast cancer cell lines. 1155 85

Hepatic ischemia/reperfusion (I/R) results in tumor necrosis factor (TNF) release. Kupffer cells (KC) are one source of this TNF. This study investigates the effects of hepatic I/R combined with lipopolysaccharide (LPS) on the lung and liver injury that follow hepatic I/R and on hepatic release of TNF, epithelial neutrophil activating protein (ENA-78), and macrophage inflammatory protein-2 (MIP-2). The effects of these experimental conditions on TNF production by primary rat KC in vitro were also investigated. Rats were subjected to hepatic I/R alone, hepatic I/R + LPS, sham laparotomy alone, or sham laparotomy + LPS and pulmonary MPO, pulmonary microvascular permeability, hepatic neutrophil influx, hepatic injury, and hepatic TNF, ENA-78, and MIP-2 production were measured. These experiments demonstrated that hepatic I/R in conjunction with LPS results in a more severe lung and liver injury and increased hepatic TNF, ENA-78, and MIP-2 release. The effects of these experimental conditions on rat KC TNF production demonstrated that hepatic I/R + LPS results in a more significant release of TNF as compared to LPS alone or I/R alone. Hepatic I/R plus LPS results in a more severe lung and liver injury and is likely secondary to a more significant and prolonged release of TNF by KC. This may provide a mechanism for development of multiple organ system failure in some patients undergoing hepatic resection, hepatic transplantation, complex vascular operations, or in the setting of hypovolemic shock. Portal endotoxemia related to mesenteric venous congestion or other systemic insults may have a significant impact on post-operative complications and recovery in the setting of a local or global hepatic I/R injury.
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PMID:Lung and liver injury following hepatic ischemia/reperfusion in the rat is increased by exogenous lipopolysaccharide which also increases hepatic TNF production in vivo and in vitro. 1158 Jan 16

Microglia are a major glial component of the central nervous system (CNS), play a critical role as resident immunocompetent and phagocytic cells in the CNS, and serve as scavenger cells in the event of infection, inflammation, trauma, ischemia, and neurodegeneration in the CNS. Studies of human microglia have been hampered by the difficulty of obtaining sufficient numbers of human microglia. One way to circumvent this difficulty is to establish permanent cell lines of human microglia. In the present study we report the generation of immortalized human microglial cell line, HMO6, from human embryonic telencephalon tissue using a retroviral vector encoding myc oncogene. The HMO6 cells exhibited cell type-specific antigens for microglia-macrophage lineage cells including CD11b (Mac-1), CD68, CD86 (B7-2), HLA-ABC, HLA-DR, and ricinus communis agglutinin lectin-1 (RCA), and actively phagocytosed latex beads. In addition, HMO6 cells showed ATP-induced responses similar to human primary microglia in Ca2+ influx spectroscopy. Both human primary microglia and HMO6 cells showed the similar cytokine gene expression in IL-1beta, IL-6, IL-8, IL-10, IL-12, IL-15, and TNF-alpha. Using HMO6 cells, we investigated whether activation was induced by Amyloid-beta fragments or lipopolysaccharide (LPS). Treatment of HMO6 cells with Amyloid-beta 25-35 fragment (Abeta(25-35)) or Amyloid-beta 1-42 fragment (Abeta(1-42)) led to increased expression of mRNA levels of cytokine/chemokine IL-8, IL-10, IL-12, MIP-1beta MIP-1, and MCP-1, and treatment with LPS produced same results. Expression of TNF-alpha and MIP1-alpha was not detected in unstimulated HMO6 cells, but their expression was later induced by long-term exposure to Abeta(25-35) or Abeta(1-42.) ELISA assays of spent culture media showed increased protein levels of TNF-alpha and IL-8 in HMO6 cells following treatment with Abeta(25-35) or LPS. Taken together, our results demonstrate that treatment of human primary microglia and HMO6 immortalized human microglia cell line with Abeta(25-35), Abeta(1-42) and LPS upregulate gene expression and protein production of proinflammatory cytokines and chemokines in these cells. The human microglial cell line HMO6 exhibits similar properties to those documented in human microglia and should have considerable utility as an in vitro model for the studies of human microglia in health and disease.
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PMID:Generation and characterization of immortalized human microglial cell lines: expression of cytokines and chemokines. 1174 1

Angiostatin effectively blocks tumor angiogenesis through still poorly understood mechanisms. Given the close association between immune and vascular regulation, we investigated the effects of angiostatin on angiogenesis-associated leukocytes. Angiostatin inhibited the migration of monocytes and, even more markedly, neutrophils. Angiostatin blocked chemotaxis of neutrophils to CXCR2 chemokine receptor agonists (IL-8, MIP-2, and GROalpha), formyl-Met-Leu-Phe (fMLP), and 12-O-tetradecanoylphorbol 13-acetate, and repressed fMLP-induced mitochondrial activity. Two different angiostatin forms (kringles 1-4 and 1-3) were effective, whereas whole plasminogen had no effect. IL-8, MIP-2, and GROalpha induced intense angiogenic reactions in vivo, but no angiogenic response to these factors was observed in neutropenic mice, demonstrating an essential role for neutrophils. Angiostatin potently inhibited chemokine-induced angiogenesis in vivo, and consistent with in vitro observations, both angiostatin forms were active and whole plasminogen had little effect. Angiostatin inhibition of angiogenesis in vivo was accompanied by a striking reduction in the number of recruited leukocytes. In vivo, the inflammatory agent lipopolysaccharide also induced extensive leukocyte infiltration and angiogenesis that were blocked by angiostatin. Neutrophils expressed mRNAs for ATP synthase and angiomotin, two known angiostatin receptors. These data show that angiostatin directly inhibits neutrophil migration and neutrophil-mediated angiogenesis and indicate that angiostatin might inhibit inflammation.
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PMID:Neutrophils as a key cellular target for angiostatin: implications for regulation of angiogenesis and inflammation. 1177 50

Dendritic cells (DCs) are professional antigen-presenting cells of the immune system and can be generated in vitro from bone-marrow cells. In this study, we systematically investigated by DNA array analysis the expression profiles of 514 immunologically relevant genes in two populations of mouse bone marrow-derived DC, immature (DC(IMAT)), and lipopolysaccharide (LPS)-stimulated mature (DC(MAT)) DCs. Our data showed that DC(IMAT) expressed transcripts for 69 (13.42% of the 514) of these genes and that, upon maturation, 32 (6.23%) of these were up-regulated and 40 (7.78%) down-regulated. Maturation-dependent up-regulation, defined by a differential expression (DE) ratio of >2, was observed among five cytokine (Flt-3L, TNF-alpha, IL-1alpha and -1beta, and IL-6), three chemokine (RANTES, MIP-2 and GROa) and three other (iNOS, MMP-13, and STRAP) genes. Reciprocally, maturation-dependent down-regulation occurred with one cytokine (IGF-1), two chemokine receptor (CCR2 and CCR5), and three other (RP105, Ax1, and UCP2) genes. Lower level, but nevertheless significantly enhanced expression of the chemokine receptor CCR7 and of NF-kappaB was also observed upon DC maturation. This DC maturation profile confirms previous findings from other lab, but it also substantially broadens our view of these cells by documenting expression changes among genes (e.g., IGF-1, MMP-13, STRAP) not reported previously in these cells.
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PMID:Analysis of the gene expression profiles of immature versus mature bone marrow-derived dendritic cells using DNA arrays. 1177 34

We have identified three novel chicken CC chemokine genes among cDNA clones derived from lipopolysaccharide-stimulated cells of the chicken macrophage cell line HD11. Two of these chemokines show DNA sequence homology to the mammalian genes SCYA20 (MIP-3alpha) and SCYA5 (RANTES), while the third shows similar levels of homology to several mammalian CC chemokines. Sequencing of genomic DNA showed that all three chicken chemokines possess the three-exon structure and conserved intron positions typical of mammalian CC chemokines. Genetic mapping of the three chicken chemokines locates them in three chromosomal regions which correspond to regions containing homologous chemokines in humans. Phylogenetic analysis of the currently known chicken and human chemokines suggests that individual chicken and human chemokines derive from common ancestral genes in patterns that reflect their genomic positions, indicating that the diversity of chemokine genes pre-dated avian-mammalian divergence. Since the function of the chemokines is principally to act as intermediates between stimulated cells and specific subsets of responding immune cells, this suggests that the complex organization of the immune system and diversity of responding cells were largely in place at that time.
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PMID:Identification, mapping, and phylogenetic analysis of three novel chicken CC chemokines. 1179 2

Recent studies demonstrated that activation of the nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP-1) by oxidant-mediated DNA damage is an important pathway of tissue injury in conditions associated with oxidative stress. Using a dual approach of PARP-1 suppression, by genetic deletion or pharmacological inhibition with the phenanthridinone PARP inhibitor PJ-34, we now demonstrate an essential role of PARP-1 in the development of pulmonary inflammation induced by lipopolysaccharide (LPS). PARP-1+/+ and PARP-1-/- mice received an intratracheal instillation of LPS (50 microg), followed after 24 h by bronchoalveolar lavage to measure the cytokines TNF-alpha, IL-1beta, and IL-6, the chemokines MIP-1alpha and MIP-2, leukocyte counts and myeloperoxidase activity (neutrophil accumulation), protein content (high permeability edema), and nitrite/ nitrate (nitric oxide production). Malondialdehyde (an index of lipid peroxidation) was measured in lung tissue. Similar experiments were conducted in BALB/c mice treated with PJ-34 or vehicle. The absence of functional PARP-1 reduced LPS-induced increases of cytokines and chemokines, alveolar neutrophil accumulation, lung hyperpermeability, NO production, and lipid peroxidation. Histological analysis revealed attenuated lung damage after PARP inhibition. Our findings support a mechanistic role of PARP-1 in the regulation of LPS-induced lung inflammation. Pharmacological inhibition of PARP may be useful in clinical conditions associated with overwhelming lung inflammation.
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PMID:Activation of poly(ADP-Ribose) polymerase-1 is a central mechanism of lipopolysaccharide-induced acute lung inflammation. 1181 23

An important feature of the pulmonary inflammatory response is that the production of certain cytokines and chemokines is largely confined to the lung. This study investigated the local and systemic responses of macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (CINC) in rats administered with either intratracheal or intravenous lipopolysaccharide (LPS). Intratracheal LPS induced a significant increase in MIP-2 in bronchoalveolar lavage (BAL) fluid with no detectable MIP-2 in the plasma. In contrast, CINC was significantly increased in both BAL fluid and the plasma after intratracheal LPS challenge. Cell-associated MIP-2 was increased in the pulmonary-recruited neutrophils (PMNs) but not in the circulating PMNs in rats given intratracheal LPS. Cell-associated CINC was increased in both the recruited and circulating PMNs in these animals. Intravenous LPS caused a marked increase in plasma MIP-2 and CINC, whereas only a small elevation of both MIP-2 and CINC concentrations in BAL fluid was observed. The lack of CINC compartmentalization compared to MIP-2 implies that these C-X-C chemokines are regulated differentially and may have different effects upon polymorphonuclear leukocyte (PMN) recruitment into the alveolar space in response to intrapulmonary LPS or bacterial challenge.
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PMID:Compartmentalization of macrophage inflammatory protein-2, but not cytokine-induced neutrophil chemoattractant, in rats challenged with intratracheal endotoxin. 1183 84

Chronic pulmonary infection with Pseudomonas aeruginosa is common in cystic fibrosis (CF) patients. P. aeruginosa lipopolysaccharide (LPS), phosholipase C (PLC), and exotoxin A (ETA) were evaluated for their ability to induce pulmonary inflammation in mice following intranasal inoculation. Both LPS and PLC induced high levels of tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta-6, gamma interferon (IFN-gamma), MIP-1 alpha MIP-2 in the lungs but did not affect IL-18 levels. ETA did not induce TNF-alpha and was a weak inducer of IL-1 beta, IL-6, macrophage inflammatory protein 1 alpha (MIP-1 alpha), and MIP-2. Remarkably, ETA reduced constitutive lung IL-18 levels. LPS was the only factor inducing IFN-gamma. LPS, PLC, and ETA all induced cell infiltration in the lungs. The role of interferon regulatory factor-1 (IRF-1) in pulmonary inflammation induced by LPS, PLC, and ETA was evaluated. When inoculated with LPS, IRF-1 gene knockout (IRF-1 KO) mice produced lower levels of TNF-alpha, IL-1 beta, and IFN-gamma than did wild-type (WT) mice. Similarly, a milder effect of ETA on IL-1 beta and IL-18 was observed for IRF-1 KO than for WT mice. In contrast, the cytokine response to PLC did not differ between WT and IRF-1 KO mice. Accordingly, LPS and ETA, but not PLC, induced expression of IRF-1 mRNA. IRF-1 deficiency had no effect on MIP-1 alpha and MIP-2 levels and on cell infiltration induced by LPS, PLC, or ETA. Flow cytometric evaluation of lung mononuclear cells revealed strongly reduced percentages of CD8(+) and NK cells in IRF-1 KO mice compared to percentages observed for WT mice. These data indicate that different virulence factors from P. aeruginosa induce pulmonary inflammation in vivo and that IRF-1 is involved in some of the cytokine responses to LPS and ETA.
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PMID:Pulmonary inflammation induced by Pseudomonas aeruginosa lipopolysaccharide, phospholipase C, and exotoxin A: role of interferon regulatory factor 1. 1185 20

Infection with Epstein-Barr virus (EBV) exerts substantially immunomodulating activities in vitro and in vivo. In this context, EBV-induced chemokine production and the influence of EBV on this highly redundant system of inflammatory proteins have hardly been investigated. This study analyzed the production of interleukin-8, RANTES, monocyte chemotactic protein-1, and macrophage inflammatory protein-1 alpha (MIP-1 alpha) on EBV infection of peripheral blood mononuclear cells from immune EBV-seropositive (EBV(+)) and noninfected EBV-seronegative (EBV(-)) individuals. EBV failed to induce the production of MIP-1 alpha in EBV(+) as well as EBV(-) individuals, whereas the other chemokines studied were readily expressed. Moreover, EBV completely down-regulated lipopolysaccharide (LPS)- and phytohemagglutinin-induced MIP-1 alpha production up to 4 hours after induction. Reverse transcription-polymerase chain reaction (RT-PCR) analysis of EBV- and LPS-stimulated cultures revealed that EBV inhibited MIP-1 alpha production on the transcriptional level. This effect was abolished by addition of antiglycoprotein (gp)350/220, a monoclonal antibody against EBV's major envelope glycoprotein, which mediates binding of the virus to the EBV receptor, CD21. However, recombinant gp350/220 protein alone did not inhibit the LPS-induced MIP-1 alpha production, indicating that infection of the target cell is indispensable for this effect. In summary, we demonstrate a new immunomodulating activity of EBV on the chemokine system that probably helps the virus to evade the host's immune system favoring lifelong infection.
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PMID:Inhibition of macrophage inflammatory protein-1 alpha production by Epstein-Barr virus. 1186 Dec 62


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