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)

Cysteine-rich intestinal protein (CRIP), a double zinc-finger LIM protein, is expressed in great abundance in the intestine. We have found comparable levels of CRIP mRNA in peritoneal macrophages, peripheral blood mononuclear cells (PBMC), and lesser amounts in thymus and spleen. Because CRIP expression was high in immune cells, rats were challenged with lipopolysaccharide (LPS) to determine whether expression was altered during the acute-phase immune response. Immunocytochemistry showed that, in adherent mononuclear cells, CRIP protein was localized in the cytoplasm. CRIP mRNA levels increased over time after LPS injection in peritoneal macrophages, PBMC, spleen, and intestine. No changes in CRIP mRNA level were seen in either liver or thymus. In PBMC, the level of CRIP mRNA decreased before increasing later in the acute-phase immune response. CRIP protein was found in the plasma. Shortly after LPS administration plasma CRIP decreased, suggesting that CRIP was either passively diffused out of capillaries or was actively shunted into tissues to execute its function. Increased CRIP expression seen in response to LPS suggests that CRIP may play a role in immune cell activation or differentiation or in processes associated with cellular repair.
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PMID:Lipopolysaccharide regulates cysteine-rich intestinal protein, a zinc-finger protein, in immune cells and plasma. 860 89

This article reviews studies of the molecular biology of the avian metallothionein (MT) genes. Analysis of cloned genes and/or cDNAs from chicken, turkey, pheasant and quail suggests that each of these species possesses a very simple MT gene family. The MT from these birds is a cysteine-rich protein of 63 amino acids that shares extensive structural homology with the mammalian MTs, and, remarkably, the deduced amino acid sequence of the major metallothionein is identical in each of these birds. The chicken MT gene is inducible by dietary or injected metal ions [i.e., zinc (Zn) and copper (Cu)], bacterial lipopolysaccharide and oxidative stress. Furthermore, it is expressed during liver development. The turkey and chicken MT genes are identical in gross structure to other functional MT genes. They consist of three exons separated by two intervening sequences. Comparisons of the nucleotide sequences of the turkey and chicken MT genes revealed regions of exceptionally high sequence conservation, suggesting important functions such as splicing, polyadenylation and transcriptional activation. Structure-function studies of the chicken MT promoter using transient transfection assays and transgenic mice have revealed cis-acting promoter sequences involved in the induction of chicken MT gene expression by metals ions. A metal-responsive enhancer was located in the proximal 107-bp of the chicken MT promoter in a region highly conserved in both the turkey and chicken MT genes. Function of this enhancer element apparently requires cooperation of transcription factors interacting with an Sp 1 binding site and a single palindromic metal-responsive element. In this regard, the structure of the proximal region of the chicken and turkey MT promoters is unique. Our current studies suggest that this enhancer regulates gene expression in a position-independent manner in transgenic mice.
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PMID:Avian metallothioneins: structure, regulation and evolution. 864 78

To determine whether lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-alpha) are involved in the induction of superoxide dismutase (SOD) in gingival tissue, we examined their effect on induction of SOD isozymes in cultured normal (NGF) and phenytoin-induced hyperplastic (PHF) gingival fibroblasts. Treatment of both NGFs and PHFs with 10 to 50 ng/mL TNF-alpha for 24 hours increased the level of manganese SOD (MnSOD) to as much as four times the level of untreated cultures. PHFs, but not NGFs, were shown to be responsive to TNF-alpha in eliciting a significant increase in copper-zinc SOD (Cu/ZnSOD), albeit in a lesser amount than MnSOD. Additionally, treatment of both types of cells with 5 to 50 mg/mL of LPS for 24 hours also elicited an increase in the levels of MnSOD. Again, an LPS-induced increase in Cu/ZnSOD levels could only be demonstrated in PHFs, but not in NGFs. These observations were further confirmed by comparing the achromatic bands associated with SOD isozymes exhibited in the electrophoretogram using a nondenaturing polyacrylamide electrophoresis technique. These results indicate that TNF-alpha and LPS were capable of inducing both MnSOD and Cu/ZnSOD simultaneously in PHF fibroblasts. PHFs may be inherently more capable than NGFs in combating oxidative stress.
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PMID:Induction of superoxide dismutase isozymes by tumor necrosis factor-alpha and lipopolysaccharide in cultured normal and hyperplastic gingival fibroblasts. 885 57

The effect of systemic zinc administration on the inflammatory hyperalgesia induced by intraplantar injections of either complete Freund's adjuvant (CFA) or bacterial endotoxin/lipopolysaccharide (LPS) in a hindpaw of adult rats was investigated. CFA injection resulted in mechanical and thermal hyperalgesia and an elevation in the levels of interleukin-1 beta (IL-1 beta) and nerve growth factor (NGF) in the ipsilateral hindpaw. Zinc treatment (20 nmole) significantly reduced sensitivity in the early phase of the inflammation and diminished the increase in the levels of IL-1 beta and NGF without affecting paw swelling. Intraplantar LPS injection also produced mechanical hyperalgesia and this too was reduced by zinc administration in a dose-dependent fashion (0.1-20 nmoles). Our results indicate that zinc has an analgesic action during early inflammation and that this may be the consequence of reducing levels of the inflammatory cytokine IL-beta and the growth factor NGF.
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PMID:Zinc reduces the hyperalgesia and upregulation of NGF and IL-1 beta produced by peripheral inflammation in the rat. 888 68

The manipulation of stress gene expression by heavy metals provides protection against the lethal effects of endotoxemia in murine models of septic shock. Recent in vitro studies with alveolar macrophages or monocytes show that induction of the stress response in these cells is followed by a decreased liberation of major cytokines [tumor necrosis factor-alpha (TNF alpha) and interleukin-1 (IL-1)] after endotoxin challenge. These findings suggest that the increased resistance to endotoxin in vivo after stress protein induction could be explained by an altered pattern of inflammatory mediator release. Therefore, we measured the time course of thromboxane-B2 (TxB2), 6-keto-PGF1 alpha, platelet activating factor (PAF), TNF alpha, interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) formation with and without induction of the stress response in an established porcine model of recurrent endotoxemia (Klosterhalfen et al., Biochem Pharmacol 43: 2103-2109, 1992). Induction of the stress response was done by a pretreatment with Zn2+ (25 mg/kg zinc-bis-(DL-hydrogenasparate = 5 mg/kg Zn2+). Pretreatment with Zn2+ prior to lipopolysaccharide (LPS) infusion induced an increased heat shock protein 70 and metallothionein expression in the lungs, liver, and kidneys and increased plasma levels of TNF alpha, IL-1 beta, IL-6, and TxB2 as opposed to untreated controls. After LPS infusion, however, pretreated animals showed significantly decreased peak plasma levels of all mediators as opposed to the untreated group. The time course of mediator release was identical with the decreasing and increasing three peak profiles described previously. Hemodynamic data presented significantly decreased peak pulmonary artery pressures and significantly altered hypodynamic/hyperdynamic cardiac output levels in the pretreated group. In conclusion, the data show that the induction of stress proteins by Zn2+ could be a practicable strategy to prevent sepsis.
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PMID:Influence of heat shock protein 70 and metallothionein induction by zinc-bis-(DL-hydrogenaspartate) on the release of inflammatory mediators in a porcine model of recurrent endotoxemia. 893 27

In neurodegenerative disease or after brain injury, parenchymal cells in the central nervous system are activated to produce inflammatory mediators, mainly consisting of cytokine-induced factors, in a manner similar to, but clearly different from a peripheral inflammatory response. The upregulated expression of several extracellular matrix proteins in astrocytes located surrounding a neuritic plaque in Alzheimer's disease is a good example of such a response. A family of mediators which is cytokine-induced during an inflammatory response in the periphery are the matrix metalloproteinases. Matrix metalloproteinases are calcium-requiring, zinc-containing endopeptidases that constitute a major component of the enzyme cascade responsible for degradation of extracellular matrix proteins such as collagen, proteoglycan and laminin. Little is known about the cellular source or the function of matrix metalloproteinases in the central nervous system or how their expression is regulated in brain. Thus, it was of interest to determine which factors of the so-called 'brain inflammatory response' regulate the expression of these proteases in the nervous system. To this end, we measured the expression of matrix metalloproteinases in cultured rat astrocytes and microglia after treatment with various cytokines. Interleukin-1 beta, tumor necrosis factor-alpha and lipopolysaccharide were potent stimulators of matrix metalloproteinase-2 (gelatinase A) and matrix metalloproteinase-9 (gelatinase B) in cultured rat astrocytes; the effect of each secretagogue was inhibited in the presence of glucocorticoid. Interleukin-1 beta and lipopolysaccharide also stimulated the production of matrix metalloproteinase-3 (stromelysin-1) in astrocytes. In addition, activated microglia release matrix metalloproteinase-9. The 'coactivator' of monocytic phagocytes, interferon-gamma, rather than augmenting the response to lipopolysaccharide, inhibited it. Thus, cytokines appear to be potent regulators of matrix metalloproteinase production in astrocytes and microglia. The presence of these enzymes in 'inflamed' central nervous system may suggest their involvement in the pathogenesis or progression of neurodegenerative diseases which are associated with an inflammatory component. Much remains to be learned about the potential substrates for these enzymes and the mechanism of their activation in the central nervous system.
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PMID:Regulation of matrix metalloproteinase expressions in astrocytes, microglia and neurons. 894 20

Matrix metalloproteinases (MMPs) are a family of Zn2+ endopeptidases that are expressed in many inflammatory conditions and that contribute to connective tissue breakdown and the release of the pro-inflammatory cytokine tumour necrosis factor-alpha (TNF-alpha). There is emerging evidence that MMPs have a role in inflammatory disorders of the central nervous system (CNS) such as multiple sclerosis. However, little is known about the expression of MMPs by inflamed tissue within the CNS or by the glia, neurones, and leucocytes which participate in the inflammatory response. To address this issue we have developed a polymerase chain reaction (PCR)-based method for the quantitation of rat MMP mRNA levels, which we have applied to astrocyte cultures with and without inflammatory stimulation. The technique relies on a competition reaction in which a synthetic standard cDNA is co-amplified with the target cDNA in the same PCR reaction. Standard multi-competitor cDNAs, containing priming sites for nine MMPs, and two housekeeping genes were constructed. We have shown that MMP activity is increased over three-fold in neonatal rat astrocyte cultures following stimulation with lipopolysaccharide (LPS). At the mRNA level, MT-MMP-1, 72 kDa gelatinase, and stromelysin-3 were constitutively expressed and unaffected by LPS treatment, whereas 92 kDa gelatinase, and stromelysin-1 were strongly induced (1,000-fold). Stromelysin-2, rat collagenase, and macrophage metalloelastase were modestly upregulated by LPS treatment. Matrilysin was not expressed. This technique is suitable for quantifying MMP expression in the cells which contribute to inflammation in the CNS and could also be applied directly to tissue samples from animal models of disease.
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PMID:Quantitation of matrix metalloproteinases in cultured rat astrocytes using the polymerase chain reaction with a multi-competitor cDNA standard. 897 1

Zinc is an important trace element for immune function. Here, we show that zinc addition in a serum- and lipopolysaccharide-free cell culture system leads to significantly enhanced levels of interleukin 1 beta (IL-1 beta) and tumour necrosis factor alpha (TNF-alpha) and to expression of the corresponding mRNA in human peripheral blood mononuclear cells (PBMC). Structurally related divalent cations like cobalt, nickel, and mercury also partially increase monokine secretion but to a much lower and thus insignificant extent. They fail to induce mRNA of TNF-alpha after 3 h of culture. Therefore, monokine induction is a zinc-specific effect influenced by the physicochemical properties of the ion. Confirmation of the unique significance of zinc for immune function provides a better understanding of the mechanisms of specific zinc-mediated immune modulation.
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PMID:Stimulation of human peripheral blood mononuclear cells by zinc and related cations. 898 Aug 78

The purpose of this study was to assess whether polymyxin B together with pentoxifylline, had beneficial effects on the acute-phase-response to E. coli endotoxin in the dwarf goat (n = 6). Polymyxin B partly neutralizes E. coli endotoxin by forming inactive polymyxin B-lipopolysaccharide (LPS) complexes; pentoxifylline has been reported to suppress the LPS-induced production of tumour necrosis factor (TNF-alpha). E. coli LPS (0.0067 microgram/kg/min over 30 min) induced fever, tachycardia, inhibition of rumen motility, a decline in WBC, lymphopenia, and decreases in plasma zinc and iron concentrations. Most of the haematological, blood biochemical and clinical effects of E. coli LPS were significantly reduced by polymyxin B pretreatment (0.1 mg/kg/min over 30 min, i.v.). Pentoxifylline (0.3 mg/kg/min over 30 min, i.v.) did not reduce the clinical and blood biochemical effects of E. coli LPS, however, it modulated the number of circulating neutrophils. No synergistic effects were observed after i.v. infusion of polymyxin B with pentoxifylline. The lack of synergy may be due to the production and release of pro-inflammatory cytokines other than TNF-alpha.
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PMID:Effects of pentoxifylline and polymyxin B on the acute-phase-response to Escherichia coli endotoxin in dwarf goats. 904 51

Under pathological conditions, the induction of nitric oxide synthase (NOS) in macrophages is responsible for NO production to a cytotoxic concentration. We have investigated changes to, and the role of, intracellular glutathione in NO production by the activated murine macrophage cell line J774. Total glutathione concentrations (reduced, GSH, plus the disulphide, GSSG) were decreased to 45% of the control 48 h after cells were activated with bacterial lipopolysaccharide plus interferon gamma. This was accompanied by a decrease in the GSH/GSSG ratio from 12:1 to 2:1. The intracellular decrease was not accounted for by either GSH or GSSG efflux; on the contrary, rapid export of glutathione in control cells was abrogated during activation. The loss of intra- and extracellular glutathione indicates either a decrease in synthesis de novo, or an increase in utilization, rather than competition for available NADPH. All changes in activated cells were prevented by pretreatment with the NOS inhibitor L-N-(1-iminoethyl)ornithine. Basal glutathione levels in J774 cells were manipulated by pretreatment with (1) buthionine sulphoximine (glutathione synthase inhibitor), (2) acivicin (gamma-glutamyltranspeptidase inhibitor), (3) bromo-octane (glutathione S-transferase substrate) and (4) diamide/zinc (thiol oxidant and glutathione reductase inhibitor). All treatments significantly decreased the output of NO following activation. The degree of inhibition was dependent on (i) duration of treatment prior to activation, (ii) rate of depletion or subsequent recovery and (iii) thiol end product. The level of GSH did not significantly affect the production of NO, after induction of NOS. Thus, glutathione redox status appears to plays an important role in NOS induction during macrophage activation.
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PMID:Induction of nitric oxide synthesis in J774 cells lowers intracellular glutathione: effect of modulated glutathione redox status on nitric oxide synthase induction. 906 66


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