UNIPROT:P43026 - FACTA Search

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Query: UNIPROT:P43026 (lipopolysaccharide)
62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumour necrosis factor (TNF), jointly referring to TNF alpha and TNF beta, is a central mediator of immune and inflammatory responses; its activities are mediated by two distinct receptors, TNFR1 (p55) and TNFR2 (p75) (reviewed in refs 1-3). The cytoplasmic domains of the TNFRs are unrelated, suggesting that they link to different intracellular signalling pathways. Although most TNF responses have been assigned to one or the other of the TNF receptors (mostly TNFR1), there is no generally accepted model for the physiological role of the two receptor types. To investigate the role of TNFR1 in beneficial and detrimental activities of TNF, we generated TNFR1-deficient mice by gene targeting. We report here that mice homozygous for a disrupted Tnfr1 allele (Tnfr1(0)) are resistant to the lethal effect of low doses of lipopolysaccharide after sensitization with D-galactosamine, but remain sensitive to high doses of lipopolysaccharide. The increased susceptibility of Tnfr1(0)/Tnfr1(0) mutant mice to infection with the facultative intracellular bacterium Listeria monocytogenes indicates an essential role of TNF in nonspecific immunity.
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PMID:Mice lacking the tumour necrosis factor receptor 1 are resistant to TNF-mediated toxicity but highly susceptible to infection by Listeria monocytogenes. 839 24

The involvement of CD14 in lipopolysaccharide (LPS) recognition and signaling has been demonstrated in several studies. For this reason, we investigated whether the resistance of Lpsd mice to LPS might be related to an impaired CD14 expression. We compared the in vivo and in vitro expression of CD14 in Lpsn (LPS sensitive) and Lpsd mice, and its modulation by LPS, killed gram-negative and gram-positive bacteria and double-stranded (ds)RNA. Untreated Lpsn and Lpsd cultured macrophages (M phi), expressed similar amounts of CD14 mRNA and membrane-bound (m)CD14. LPS enhanced CD14 expression only in Lpsn M phi, while all bacteria, or dsRNA, enhanced CD14 in Lpsn and Lpsd M phi. Similarly, in vivo administration of LPS induced or enhanced CD14 mRNA in different organs of Lpsn mice only, while bacteria or dsRNA in both types of mouse. Furthermore, exogenous recombinant tumor necrosis factor (TNF) induced in vivo and in vitro enhanced CD14 expression in Lpsn, Lpsd and also in TNF receptor 2-deficient (TNFR2-/-) mice, but failed to do so in TNFR1-/- mice, showing that TNFR1 mediates the effect of TNF on CD14. However, LPS, bacteria and dsRNA induced CD14 in both TNFR2-/- and TNFR1-/- mice to a similar extent, revealing that this induction does not require TNF signaling.
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PMID:Induction of CD14 expression in Lpsn, Lpsd and tumor necrosis factor receptor-deficient mice. 892 56

Tumor necrosis factor (TNF) is a central mediator of immune and inflammatory responses. Its activities have been shown to be mediated by two distinct receptors, TNFR1 (p55) and TNFR2 (p75). The cytoplasmic domains of both TNF receptors are unrelated, suggesting that they link to different intracellular signaling pathways. To determine their role in vivo in lipopolysaccharide (LPS)- and TNF-induced skin inflammatory necrosis, TNFR1-, TNFR2-, and TNF lymphotoxin-alpha (LT alpha)-deficient mice were used. Skin abscesses were experimentally induced with local application of TNF or LPS. Large macroscopic ulcerations were observed in TNF-injected wild-type animals and to a slightly lesser extent in TNFR2-deficient mice with tissue destruction in both cases extending deep into the dermis. Tissue destruction was accompanied by an intense immune infiltrate composed mainly of neutrophils, lymphocytes, and macrophages. TNFR1-deficient and TNFR1/TNFR2-double-deficient mice, however, did not exhibit any ulceration and showed only a very mild inflammatory infiltrate. In TNF/LT alpha-double ligand0-deficient animals, a moderate epidermal necrosis was observed with a reduced inflammatory infiltrate compared to wild-type animals. As with TNF injections, subcutaneous injection of LPS induced a comparable pattern of skin necrosis in wild-type and TNF receptor mutant mice, yet a slightly more acute inflammatory level was observed regardless of the type of animal tested. As found for TNF-induced skin necrosis, the extent of LPS-induced skin necrosis was reduced in TNF/LT alpha-deficient mice compared to wild-type animals. The present data strongly suggest that TNFR1, rather than TNFR2, is engaged in LPS- and TNF-induced skin necrosis and highlight the predominant role played by TNF in LPS-induced inflammatory diseases.
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PMID:Tumor necrosis factor (TNF)-induced cutaneous necrosis is mediated by TNF receptor 1. 914 75

Metallothioneins (MTs) are a family of low molecular weight proteins which in rodents is comprised of several isoforms (MT-I to MT-IV). MT-I and MT-II are widely expressed isoforms, whereas MT-III is mainly expressed in the central nervous system and is the only isoform that inhibits survival and neurite formation of rat cortical neurons in vitro. However, the physiological roles and regulation of these proteins in the brain are poorly characterized. In this report we have studied the putative role of IL-6 and TNF-alpha on the regulation of brain MT-I and MT-III, by using mice carrying a null mutation in the IL-6 or the TNF-alpha type 1 receptor genes or both. In situ hybridization analysis revealed that brain MT-I induction by bacterial lipopolysaccharide (LPS) was significantly lower in IL-6- and TNFR1-deficient mice, and to a greater extent in the double mutant mice, in most brain areas studied. These results suggest that the MT-I isoform could be considered an acute-phase protein in the brain, which is consistent with previous studies in transgenic mice overexpressing IL-6 in astrocytes. In contrast to LPS, brain MT-I induction by restraint stress was not affected significantly by IL-6 or TNFR1 deficiencies, suggesting that these cytokines are not important during the stress response in the brain. In basal conditions, it was also observed that the double mutant mice had diminished MT-I mRNA levels in several brain areas. In contrast to MT-I, MT-III mRNA levels were minimally affected by either LPS or stress. Yet, significant decreasing effects of IL-6 and TNFR1 deficiencies were observed in the Purkinje neuronal layer of the cerebellum (after LPS) and ependymal cells (after LPS and stress). In contrast, significant increasing effects, especially of TNFR1 deficiency, were observed in CA1 hippocampal area, retrosplenial and parietal cortex, and in thalamic nuclei (after LPS). These results demonstrate that IL-6 and TNF-alpha are involved in brain MTs regulation during LPS-elicited inflammatory response but not during the stress response.
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PMID:Interleukin-6 and tumor necrosis factor-alpha type 1 receptor deficient mice reveal a role of IL-6 and TNF-alpha on brain metallothionein-I and -III regulation. 967 20

To determine the roles of the type 1 tumor necrosis factor (TNF) receptor (TNFR1) in lung inflammation and antibacterial defense, we exposed transgenic mice lacking TNFR1 [TNFR1(-/-)] and wild-type control mice to aerosolized lipopolysaccharide or Pseudomonas aeruginosa. After LPS, bronchoalveolar lavage fluid (BALF) from TNFR1(-/-) mice contained fewer neutrophils and less macrophage inflammatory protein-2 than BALF from control mice. TNF-alpha, interleukin-1beta, and total protein levels in BALF as well as tissue intercellular adhesion molecule-1 expression did not differ between the two groups. In contrast, lung inflammation and bacterial clearance after infection were augmented in TNFR1(-/-) mice. BALF from infected TNFR1(-/-) mice contained more neutrophils and TNF-alpha and less interleukin-1beta and macrophage inflammatory protein-2 than that from control mice, but protein levels were similarly elevated in both groups. Lung inflammation and bacterial clearance were also augmented in mice lacking both TNF receptors. Thus TNFR1 facilitates neutrophil recruitment after inhalation of lipopolysaccharide, in part by augmenting chemokine induction. In contrast, TNFR1 attenuates lung inflammation in response to live bacteria but does not contribute to increased lung permeability and is not required for the elimination of P. aeruginosa.
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PMID:Role of the type 1 TNF receptor in lung inflammation after inhalation of endotoxin or Pseudomonas aeruginosa. 1033 27

Normal human lung fibroblasts downregulate the production of tumor necrosis factor (TNF)-alpha by activated monocytes through the production of prostaglandin E(2) (PGE(2)), contributing to the local control of the inflammatory process. In this study, we provide evidence that fibroblasts derived from diseased tissue, such as fibrotic lung fibroblasts, exhibit different functional features compared with normal cells, with particular regard to their modulatory role. Indeed, fibrotic fibroblasts (FF) spontaneously produced less PGE(2) (3,300 +/- 410 pg/ml) compared with normal fibroblasts (NF) (7,500 +/- 270 pg/ml) and, as a consequence, they showed a reduced ability to downregulate the production of TNF-alpha by lipopolysaccharide (LPS)- activated monocytes. The percentage of inhibition induced by normal cells on the production of TNF-alpha by LPS-activated monocytes was 61 +/- 5.9%, whereas the inhibitory effect exerted by fibrotic cells was reduced to 32 +/- 4% (P < 0.01). We have also observed that the ability of TNF-alpha to induce PGE(2) was impaired in FF and was related to a reduced expression of cyclooxygenase 2. This was possibly due to the reduction of the expression of TNF receptors (TNFRs) in fibrotic cell lines compared with normal cell lines. Flow cytometry revealed that the mean fluorescence intensity (MFI) of both isoforms of TNFR was significantly lower in FF compared with NF. The MFI of TNFR1 was 3. 55 +/- 0.12 for NF and 1.78 +/- 0.35 for FF (P < 0.001). The MFI of TNFR2 was 1.95 +/- 0.27 for NF and 0.99 +/- 0.16 for FF (P < 0.01). The analysis of the effect of TNF-alpha on some functions associated with collagen metabolism in NF and FF showed an increase of the expression of the receptor for collagen type I (alpha(2)beta(1) integrin) in NF (42 +/- 10%) and an even larger increase in FF (102 +/- 23%) (P < 0.05). Interestingly, unlike NF, TNF-alpha failed to increase matrix metalloproteinase 1 levels in FF and did not cause any growth inhibition in these cells. The reduced capability of fibrotic cells to produce PGE(2) either spontaneously or after TNF-alpha treatment may lead to an unrestrained release of TNF-alpha from activated monocytes and, as a result of the reduced expression of TNFRs, to a different response of these cells to TNF-alpha. These changes may be important in the evolution of the inflammatory process, potentially contributing to its transformation into a chronic and self-perpetuating process.
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PMID:Different expression of TNF-alpha receptors and prostaglandin E(2 )Production in normal and fibrotic lung fibroblasts: potential implications for the evolution of the inflammatory process. 1078 36

Analysis of gene expression in a mouse model of unilateral ureteral obstruction (UUO) revealed significant induction of CD14 mRNA in kidneys with obstructed ureters. Immunocytochemical analysis indicated that CD14 was upregulated in tubular epithelial cells and this upregulation was not attributable to infiltration of the kidneys by mononuclear cells. This induction of CD14 mRNA was found to occur in BALB/C, C57BL/6, C3H/HeN, and C3H/HeJ mice during UUO. Ischemia/reperfusion of kidneys also induced CD14 mRNA. Mice lacking either of the tumor necrosis factor-alpha receptor (TNFR) genes were also studied; the induction of CD14 was blunted in TNFR 1-knockout mice but not in TNFR2-knockout mice. Apoptosis of tubular cells in lipopolysaccharide-resistant CH3/HeJ mice was significantly (P: < 0. 05) less than that in lipopolysaccharide-responsive CH3/HeN mice during UUO. These results suggest that CD14 is acutely induced in tubular epithelial cells in two mouse models of renal injury. This induction is regulated by tumor necrosis factor-alpha, through TNFR1. CD14 may participate in the apoptosis of tubular epithelial cells on a more chronic basis by activating a pathway that is absent or deficient in C3H/HeJ mice.
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PMID:Induction of CD14 in tubular epithelial cells during kidney disease. 1096 93

We demonstrated that 4 mM butyrate induces apoptosis in murine peritoneal macrophages in a dose- and time-dependent manner as indicated by studies of cell viability, flow cytometric analysis of annexin-V binding, DNA ladder pattern and the determination of hypodiploid DNA content. The activity of caspase-3 was enhanced during macrophage apoptosis induced by butyrate and the caspase inhibitor z-VAD-FMK (100 microM) inhibited the butyrate effect, indicating the major role of the caspase cascade in the process. The levels of butyrate-induced apoptosis in macrophages were enhanced by co-treatment with 1 microg/ml bacterial lipopolysaccharide (LPS). However, our data indicate that apoptosis induced by butyrate and LPS involves different mechanisms. Thus, LPS-induced apoptosis was only observed when macrophages were primed with IFN-gamma and was partially dependent on iNOS, TNFR1 and IRF-1 functions as determined in experiments employing macrophages from various knockout mice. In contrast, butyrate-induced macrophage apoptosis was highly independent of IFN-gamma priming and of iNOS, TNFR1 and IRF-1 functions.
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PMID:Butyrate induces apoptosis in murine macrophages via caspase-3, but independent of autocrine synthesis of tumor necrosis factor and nitric oxide. 1184 19

We investigated the requirement for tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1 receptors in the pathogenesis of the pulmonary and hepatic responses to Escherichia coli lipopolysaccharide (LPS) by studying wild-type mice and mice deficient in TNF type 1 receptor [TNFR1 knockout (KO)] or both TNF type 1 and IL-1 receptors (TNFR1/IL-1R KO). In lung tissue, NF-kappaB activation was similar among the groups after exposure to aerosolized LPS. After intraperitoneal injection of LPS, NF-kappaB activation in liver was attenuated in TNFR1 KO mice and further diminished in TNFR1/IL-1R KO mice; however, in lung tissue, no impairment in NF-kappaB activation was found in TNFR1 KO mice and only a modest decrease was found in TNFR1/IL-1R KO mice. Lung concentrations of KC and macrophage-inflammatory peptide 2 were lower in TNFR1 KO and TNFR1/IL-1R KO mice after aerosolized and intraperitoneal LPS. We conclude that LPS-induced NF-kappaB activation in liver is mediated through TNF-alpha- and IL-1 receptor-dependent pathways, but, in the lung, LPS-induced NF-kappaB activation is largely independent of these receptors.
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PMID:Modulation of endotoxin-induced NF-kappa B activation in lung and liver through TNF type 1 and IL-1 receptors. 1238 56

Calagualine derived from the fern of the genus Polypodium, commonly called calaguala, has had clinically documented medicinal uses in South America and Spain and been shown to block tumor metastasis, proliferation, and inflammation, all known to require the activation of nuclear transcription factor-kappaB (NF-kappaB). Therefore, we investigated the effect of calagualine on NF-kappaB activation induced by various inflammatory and tumor promoting agents. Calagualine blocked tumor necrosis factor (TNF)-induced activation of NF-kappaB through inhibition of phosphorylation and degradation of IkappaBalpha, an inhibitor of NF-kappaB. The effects of calagualine were not cell type-specific, as it blocked TNF-induced NF-kappaB activation in a variety of cells. NF-kappaB-dependent reporter gene transcription activated by TNF was also suppressed by calagualine. The TNF-induced NF-kappaB activation cascade involving TNFR1-TNF receptor-associated death domain-TNF receptor-associated factor 2 (TRAF2)-NF-kappaB-inducing kinase (NIK)-IkappaBalpha kinase was interrupted at the TRAF2 and NIK sites by calagualine, which would account for its suppression of NF-kappaB reporter gene expression. Calagualine blocked NF-kappaB activation induced by phorbol ester and lipopolysaccharide. Overall our results indicate that calagualine inhibits activation of NF-kappaB and this may provide a molecular basis for calagualine's ability to suppress inflammation and tumorigenesis.
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PMID:Calagualine inhibits nuclear transcription factors-kappaB activated by various inflammatory and tumor promoting agents. 1256 72

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