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

The Ras signalling pathway targets transcription factors such as the ternary complex factors that are recruited by the serum response factor to form complexes on the serum response element (SRE) of the fos promoter. We have identified a new ternary complex factor, Net-b. We report the features of the net gene and show that it produces several splice variants, net-b and net-c. net-b RNA and protein are expressed in a variety of tissues and cell lines. net-c RNA is expressed at low levels, and the protein was not detected, raising the possibility that it is a cryptic splice variant. We have studied the composition of ternary complexes that form on the SRE of the fos promoter with extracts from fibroblasts (NIH 3T3) cultured under various conditions and pre-B cells (70Z/3) before and after differentiation with lipopolysaccharide (LPS). The fibroblast complexes contain mainly Net-b followed by Sap1 and Elk1. Net-b complexes, as well as Sap1 and Elk1, are induced by epidermal growth factor (EGF) stimulation of cells cultured in low serum. Pre-B-cell complexes contain mainly Sap1, with less of Net-b and little of Elk1. There is little change upon LPS-induced differentiation compared to the increase with EGF in fibroblasts. We have also found that Net-b is a nuclear protein that constitutively represses transcription. Net-b is not activated by Ras signalling, in contrast to Net, Sap1a, and Elk1. We have previously reported that down-regulation of Net proteins with antisense RNA increases SRE activity. The increase in SRE activity is observed at low serum levels and is even greater after serum stimulation, showing that the SRE is under negative regulation by Net proteins and the level of repression increases during induction. Net-b, the predominant factor in ternary complexes in fibroblasts, may both keep the activity of the SRE low in the absence of strong inducing conditions and rapidly shut the activity off after stimulation.
 ...
PMID:Net-b, a Ras-insensitive factor that forms ternary complexes with serum response factor on the serum response element of the fos promoter. 931 25

Keratinocyte growth factor (KGF) promotes epithelial growth and differentiation and has potent effects on the liver. The coinjection of lipopolysaccharide (LPS) and D-galactosamine (GalN) results in hepatic failure in mice. Mechanistically, LPS-induced tumor necrosis factor (TNF) triggers hepatocyte apoptosis, which is enhanced by GalN-arrested transcription. Similarly, the combination of TNF and actinomycin D (ActD) causes hepatocyte apoptosis in vitro. We studied the effect of KGF on LPS and GalN-induced hepatic failure in vivo and on TNF- and ActD-induced hepatocyte apoptosis in vitro, where it was compared with those of hepatic growth factor (HGF) and epidermal growth factor (EGF). Mice treated with human recombinant KGF (1 mg/kg subcutaneously) 24 hours before intraperitoneal coinjection of LPS and GalN sustained prolonged survival compared with control mice, although overall mortality was not changed. The counts of apoptotic hepatocytes, serum alanine and aspartate transaminases, and DNA fragments in the cytosolic fraction of liver homogenates were higher in control mice than in treated mice 6 hours after LPS and GalN coinjection, before any mortality occurred. In vitro, hepatocytes pretreated with KGF exhibited reduced TNF- and ActD-induced cell damage and DNA fragmentation, similar to hepatocytes pretreated with HGF and EGF. In conclusion, KGF prolongs survival during LPS- and GalN-induced hepatic failure by temporarily protecting hepatocytes against apoptosis. It also protects hepatocytes in vitro against TNF- and ActD-induced apoptosis.
 ...
PMID:Keratinocyte growth factor protects murine hepatocytes from tumor necrosis factor-induced apoptosis in vivo and in vitro. 962 Mar 31

CD14-transfected Chinese hamster ovary K1 fibroblasts (CHO/CD14) respond to lipopolysaccharide (LPS) by metabolizing arachidonic acid and with translocation of NF-kappaB to the nucleus. Although previous experiments failed to identify the production of tumor necrosis factor-alpha and interleukin (IL)-1beta by CHO/CD14 cells, LPS did induce the expression of IL-6 mRNA and the subsequent release of the IL-6 protein. To identify additional LPS-inducible genes, a cDNA library derived from LPS-stimulated CHO/CD14 cells was screened by subtractive hybridization. Fourteen genes were found to be expressed differentially, and two were analyzed in detail: hop (Hsp70/Hsp90-organizing protein), which is the hamster homologue of the stress-inducible yeast gene, STI1, and clone H411, which encodes a novel LPS-inducible growth factor. In response to LPS, the expression of Hop mRNA was also increased in both the murine macrophage cell line, RAW 264.7, as well as in primary hamster macrophages. This suggested that the up-regulation of Hop expression is part of the macrophage stress response to LPS. Clone H411 encodes a protein in the epidermal growth factor-like repeat protein family. Overexpression of H411 cDNA in the RAW 264.7 macrophage cell line promoted an increased growth rate, suggesting that expression of H411 is part of the proliferative cell response to LPS. Both Hop and H411 represent novel gene products not previously recognized as part of the complex biological response to endotoxin.
 ...
PMID:Bacterial lipopolysaccharide induces expression of the stress response genes hop and H411. 1040 56

Generation of reactive oxygen species (ROS) in A431 cells, NIH3T3 fibroblasts expressing normal epidermal growth factor (EGF) receptor, L929 fibroblasts, and in mouse peritoneal macrophages (professionally phagocytic cells) upon the effect of different activators has been studied. It has been shown that ROS formation in A431 and NIH3T3 cells upon the effect of EGF is time- and dose-dependent process. A variety of stimuli were used to stimulate macrophage ROS production. However, the effect of only phorbol ester, opsonized zymozan, peptide fMLP, and platelet activating factor led to ROS generation, whereas tumor necrosis factor alpha, interferon gamma, and lipopolysaccharide did not stimulate macrophage oxidative burst. The literature data on ROS generation in a variety of cell types are presented. ROS formed in cells acted upon certain agents are considered as the molecules participating in intracellular signaling.
 ...
PMID:[Post-receptor formation of active forms of oxygen in nonphagocytic cells]. 1049 12

The endothelin-1 (ET-1) concentrations were measured by RIA in the media of confluent monolayer cultures of rat articular chondrocyte (RAC) exposed to fetal calf serum (FCS) and several growth factors and cytokines. The cells were obtained from 1- and 18-month-old rats. First passage cells were starved in Dulbecco's modified Eagle's medium (DMEM) containing 0.2% FCS serum for 24 h and then incubated for 48 h in the same fresh medium with each of the following factors: fetal calf serum (FCS), transforming growth factor-beta (TGF-beta), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1), interleukin-1 beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), lipopolysaccharide (LPS), and NO donor, sodium nitroprusside (SNP). The following was found: the cells from 18-month-old animals accumulated about twice as much ET-1 per microg DNA under basal (low serum) and stimulated conditions as cells from young rats. All, but PDGF and SNP produced concentration-dependent rise in ET-1 levels, the most effective being 10% FCS, IL-1beta, TNF-alpha, EGF, IGF-1 and LPS. TGF-beta caused the smallest stimulation and PDGF was ineffective or slightly inhibitory at high concentrations. SNP caused concentration-dependent decrease of ET-1 concentrations. ET-1-specific mRNA was identified by RT-PCR in cells incubated with the above factors and its concentration paralleled that of the peptide. This suggests that ET-1 found in the culture media of RAC stems, at least in part, from the synthesis. Increased immunoreactive peptide concentration and mRNA expression with the age of the donor rat and its regulation by several growth factors and cytokines suggest the involvement of ET-1 in chondrocytes' physiology and possibly pathology.
 ...
PMID:Endothelin-1 in monolayer cultures of articular chondrocytes from young and old rats: regulation by growth factors and cytokines. 1073 80

The hepatoprotecive effects of recombinant human epidermal growth factor (hEGF) on chemically and immunologically induced experimental liver injury models were examined. The hEGF clearly decreased serum transaminase levels in D-galactosamine (D-GalN) and D-GalN/lipopolysaccharide (LPS)-induced liver injury models under sub-lethal conditions. However, it has not significantly changed either serum or in vitro tumor necrosis factor (TNF)-alpha production or in vitro nitric oxide (NO) production, suggesting that the hepatoprotection by EGF is not mediated by inhibiting these pathological mediators produced in D-GalN and D-GalN/LPS-induced liver injury.
 ...
PMID:Hepatoprotection by human epidermal growth factor (hEGF) against experimental hepatitis induced by D-galactosamine (D-galN) or D-GalN/lipopolysaccharide. 1104 Dec 60

Placental inflammations (villitis) are accompanied by loss of the syncytiotrophoblast, which is the cellular barrier separating maternal blood from fetal tissue in the villous placenta. We propose that syncytiotrophoblast loss is mediated by adhesion of activated maternal monocytes. This hypothesis was tested with a co-culture model of peripheral blood monocytes and placental syncytiotrophoblasts. We find that LPS-activated monocytes adhere to interferon-gamma (IFN-gamma)-treated syncytiotrophoblasts via monocyte LFA-1 for >48 h, during which time the monocytes induce trophoblast apoptosis and subsequent damage of the trophoblast layer. Optimal monocyte-mediated syncytiotrophoblast death requires both lipopolysaccharide (LPS) and IFN-gamma and is inhibited by either anti-tumor necrosis factor (TNF) antibody or epidermal growth factor. Syncytiotrophoblast damage is largely limited to culture surfaces in the vicinity of bound monocytes. These results show that activated maternal monocytes bound to the placental barrier can induce focal damage mediated by the inflammatory cytokine TNF-alpha and suggest a route for maternal leukocyte infiltration into the fetal stroma.
 ...
PMID:Monocytes adhering by LFA-1 to placental syncytiotrophoblasts induce local apoptosis via release of TNF-alpha. A model for hematogenous initiation of placental inflammations. 1112 59

CD14-expressing Chinese hamster ovary (CD14-CHO) cells, established by transfection of human CD14 DNA, acquired high responsiveness to lipopolysaccharide (LPS) through membrane-bound CD14 expression. LPS induced DNA synthesis and activated a series of mitogen-activated protein (MAP) kinases, extracellular signal-regulated kinase 1/2 (Erk1/2), p38, and c-Jun N-terminal kinase/stress-activated protein kinase, in CD14-CHO cells but not in mock-transfected CHO cells. Anti-CD14 antibody completely abrogated both LPS-induced DNA synthesis and LPS-induced phosphorylation of those MAP kinases, suggesting a critical role of membrane-bound CD14 in LPS signaling. A p38 MAP kinase inhibitor, SB203580, markedly augmented LPS-induced DNA synthesis in CD14-CHO cells, whereas an Erk1/2 inhibitor, PD98059, had no affect. On the other hand, SB203580 exhibited no effect on epidermal growth factor-induced DNA synthesis in CD14-CHO cells, although PD98059 inhibited it significantly. The activation and inactivation of p38 MAP kinase with dominant negative and dominant positive mutants also suggested the participation of p38 MAP kinase in LPS-induced DNA synthesis. It was therefore suggested that the activation of p38 MAP kinase can negatively regulate LPS-induced cell proliferation in CD14-CHO cells.
 ...
PMID:Inhibition of p38 mitogen-activated protein kinase augments lipopolysaccharide-induced cell proliferation in CD14-expressing Chinese hamster ovary cells. 1115 88

Endotoxin [lipopolysaccharide (LPS)] and some cytokines are known to induce tissue factors with the expression of procoagulant activity (PCA) on the cell surface of endothelial cells. We established a modified quantitative procedure for PCA expressed on the cell surface, and studied the effects of serum and epidermal growth factor (EGF) on the LPS-induced activation of PCA on cultured human umbilical vein endothelial cells. Meanwhile, human umbilical cord serum elevated PCA more than either fetal bovine serum (FBS) or human adult serum. Generally, the existence of LPS raises the concentration of EGF in the blood, since monocytes and other types of cells express EGF and release it into the vessel by LPS stimulation. Although 10 ng/ml EGF did not induce PCA even in the presence of 10% FBS, it enhanced LPS-induced PCA under the same conditions. In the presence of 10% FBS, PCA induced both by LPS alone and by LPS + EGF was reduced the same amount by the protein kinase C (PKC) inhibitors H7 and H8. These results suggest that the serum contains some cofactor other than EGF, and that EGF enhanced this LPS-induced PCA independent of the cofactor through PKC-involved signaling.
 ...
PMID:Epidermal growth factor enhances lipopolysaccharide-induced procoagulant activity on the cell surface of endothelial cells. 1150 82

The lipoxygenase pathway has been implicated in the growth, migration, and contraction of vascular smooth muscle cells (VSMCs). However, the precise type of lipoxygenase present in the vascular wall has not been characterized. In this study, we used a specific reverse-transcriptase polymerase chain reaction method with 2 sets of specific primers on total RNA and polyA (+)RNA of normal human VSMCs prepared from umbilical artery. Two forms of platelet-type 12-lipoxygenase mRNA were present in human VSMCs: the already published form cloned from human erythroleukemia cells and a variant form of platelet-type 12-lipoxygenase, which includes 2 additional sequences consistent with the 2 introns (D and E). This novel form of 12-lipoxygenase poly A (+)RNA was downregulated by lipopolysaccharide (10 ug/ml) and upregulated by epidermal growth factor (100 ng/ml) but was not affected by angiotensin II (10(-7) mol/l). We developed a rabbit anti-human platelet-type 12-lipoxygenase polyclonal antibody directed against a 24-amino acid peptide encoded within exon 4. Western immunoblotting of protein extracted from VSMCs and umbilical artery and platelet extract with this antibody showed a coordinate 110-kDa protein and the already-described 70-kDa band detected in platelets and cord homogenate. Another 120-kDa protein was consistently detected in cord extracts but not in platelet or VSMC homogenates. The immunohistochemistry study performed with the same antibody showed extensive cytoplasmic staining of VSMCs. The specific role of these different forms of platelet-type 12-lipoxygenase is subject to further investigation.
 ...
PMID:A novel form of platelet-type 12-lipoxygenase mRNA in human vascular smooth muscle cells. 1164


<< Previous 1 2 3 4 5 6 7 8 9 Next >>