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)

gp49B1 is expressed on mast cells and inhibits immunoglobulin E-dependent activation and inflammation in vivo. We now show that gp49B1 is expressed on neutrophils and prevents neutrophil-dependent vascular injury in response to lipopolysaccharide (LPS). The intradermal (i.d.) injection of LPS into gp49B1-null (gp49B-/-) but not gp49B1-sufficient (gp49B+/+) mice elicited macroscopic hemorrhages by 24 h, which were preceded on microscopic analyses by significantly more intravascular thrombi (consisting of neutrophils, platelets, and fibrin) that occluded venules and by more tissue neutrophils than in gp49B+/+ mice. However, there were no differences in the number of intact (nondegranulating) mast cells or the tissue levels of mediators that promote neutrophil recruitment. Hemorrhage was prevented by depleting neutrophils, blocking beta2 integrin-intercellular adhesion molecule 1 interactions, or inhibiting coagulation. These characteristics indicate that gp49B-/- mice are exquisitely sensitive to a local Shwartzman reaction (LSR) after a single i.d. injection of LPS, whereas in the classic LSR, a second exposure is required for increased beta2 integrin function, intravascular neutrophil aggregation, formation of occlusive thrombi, and hemorrhage. Moreover, LPS increased gp49B1 expression on neutrophils in vivo. The results suggest that gp49B1 suppresses the LPS-induced increase in intravascular neutrophil adhesion, thereby providing critical innate protection against a pathologic response to a bacterial component.
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PMID:Prevention of lipopolysaccharide-induced microangiopathy by gp49B1: evidence for an important role for gp49B1 expression on neutrophils. 1455 14

Cold preservation and reperfusion of liver during transplantation are necessary steps in the procedure but which are also associated with damage to the organ. One aspect of this damage is thought to concern up-regulation of inflammatory markers, such as the adhesion molecule intercellular adhesion molecule 1 (ICAM-1) on target cells in the liver. This aids sequestration of activated leucocytes, which promote inflammation, by a complex sequence of events, including free radical mediated damage. We have studied changes in ICAM-1 in rat liver as a consequence of cold preservation for various times, and also after warm reperfusion during isolated liver perfusion. We have also investigated the effects of the free radical scavenging agent (reduced glutathione-GSH) on the modulation of ICAM-1 expression after cold hypoxia and reperfusion. Livers were subjected to various regimes of cold preservation and reperfusion. Liver biopsies were taken at three time points (initial baseline on liver exposure; after organ flushing and post-storage at 0, 8, 16, and 24h cold hypoxia in University of Wisconsin solution; in the same livers after 1h warm reperfusion). The tissues were processed for frozen biopsy work, and frozen sections were stained using immunohistochemical methods, for blinded scoring by an independent observer. Positive controls were obtained by exposure to endotoxin lipopolysaccharide before liver flushing. ICAM-1 expression was low in control livers (0.33+/-0.21), and increased to near maximal (2.83+/-0.17) after endotoxin exposure. ICAM-1 expression increased progressively with cold preservation, reaching values of 1.17+/-0.31 and 1.83+/-0.31 after 16 and 24h, respectively (P<0.05 and 0.02 versus controls). Warm reperfusuion increased ICAM-1 expression in all flushed groups and with longer cold preservation was close to maximal (2.67+/-0.21 after 16h and 2.98+/-0.02 after 24h; P<0.001 in both cases). Addition of the free radical scavenger GSH prevented up-regulation of ICAM-1 in livers reperfused after flushing and cold storage for up to 8h; beyond this time, ICAM-1 expression still increased, such that by 24h cold preservation and reperfusion absence (2.98+/-0.02) or presence (2.67+/-0.21) made no difference. We conclude that liver ICAM-1 expression is demonstrably increased by progressive cold preservation and reperfusion, and is only marginally affected by addition of GSH during reperfusion. The model can be used to investigate other agents which might be more successful in preventing post-storage inflammatory damage.
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PMID:Hepatic cold hypoxia and oxidative stress: implications for ICAM-1 expression and modulation by glutathione during experimental isolated liver preservation. 1458 Aug 50

To investigate the status of soluble adhesion molecules (sAMs) during aging, the present study determined protein levels of several major sAMs in serum samples obtained from rats at different ages. These sAMs include E-selectin, P-selectin, vascular cell adhesion molecule 1 (VCAM-1), and intercellular adhesion molecule 1 (ICAM-1). Fischer 344 rats, ages 6, 12, 18, and 24 months, fed ad libitum (AL) and calorie restricted (CR) diets were used in this study. Analysis by Western blotting showed that the levels of all sAMs studied increased during aging in AL rats, but were effectively blunted in the CR rats. Total reactive oxygen species/reactive nitrogen species (ROS/RNS) levels were measured by fluorescent probe 2',7'-dichlorofluorescin diacetate. Increased ROS/RNS levels were found to coincide with increased levels of superoxide-generating xanthine oxidase in serum during aging, but were found suppressed by CR. Increases in sAMs levels were duplicated in another experiment in which young (13-month-old) and old (31-month-old) rats were injected with proinflammatory lipopolysaccharide. These findings suggest that the altered expressions of sAMs may be due to increased oxidative stress with advanced age and that these increases were prevented by CR through its antioxidative action.
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PMID:Alteration of soluble adhesion molecules during aging and their modulation by calorie restriction. 1468 95

Genes encoding proteins with PYRIN/PAAD/DAPIN domains, a nucleotide binding fold (NACHT), and leucine rich repeats have recently been recognized as important mediators in autoimmune inflammatory disorders. Here we characterize the expression and function of a member of the PYRIN and NACHT domain (PAN) family, PAN1 (also known as NALP2 and PYPAF2). PAN1 protein expression is regulated by lipopolysaccharide (LPS) and interferons (IFNbeta and IFNgamma) in THP-1 macrophage cells. In gene transfection studies PAN1 manifests an inhibitory influence on NF-kappaB activation induced by various pro-inflammatory stimuli, including tumor necrosis factor TNFalpha and interleukin-1beta (IL-1beta). Gene transfer-mediated elevations in PAN1 protein also suppressed activation of IkappaB kinases induced by inflammatory cytokines. Conversely, reducing endogenous levels of PAN1 using small interfering RNA enhanced LPS-induced production of ICAM-1 (intercellular adhesion molecule 1), an NF-kappaB-dependent gene. We also show here that PAN1 binds via its PYRIN domain to ASC, an adapter protein involved in caspase-1 activation. This binding is disrupted by mutation of the alpha1 helix of ASC. In gene transfer experiments PAN1 enhances caspase-1 activation and IL-1beta secretion in collaboration with ASC. Conversely, reducing endogenous levels of PAN1 using small interfering RNA significantly reduced LPS-induced secretion of IL-1beta in monocytes. We propose that PAN1 functions as a modulator of the activation of NF-kappaB and pro-caspase-1 in macrophages.
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PMID:PAN1/NALP2/PYPAF2, an inducible inflammatory mediator that regulates NF-kappaB and caspase-1 activation in macrophages. 1545 91

Exosomes are secreted vesicles formed in late endocytic compartments. Immature dendritic cells (DCs) secrete exosomes, which transfer functional major histocompatibility complex (MHC)-peptide complexes to other DCs. Since immature and mature DCs induce different functional T-cell responses (ie, tolerance versus priming), we asked whether DC maturation also influenced the priming abilities of their exosomes. We show that exosomes secreted by lipopolysaccharide (LPS)-treated mature DCs are 50- to 100-fold more potent to induce antigen-specific T-cell activation in vitro than exosomes from immature DCs. In vitro, exosomes from mature DCs transfer to B lymphocytes the ability to prime naive T cells. In vivo, only mature exosomes trigger effector T-cell responses, leading to fast skin graft rejection. Proteomic and biochemical analyses revealed that mature exosomes are enriched in MHC class II, B7.2, intercellular adhesion molecule 1 (ICAM-1), and bear little milk-fat globule-epidermal growth factor-factor VIII (MFG-E8) as compared with immature exosomes. Functional analysis using DC-derived exosomes from knock-out mice showed that MHC class II and ICAM-1 are required for mature exosomes to prime naive T cells, whereas B7.2 and MFG-E8 are dispensable. Therefore, changes in protein composition and priming abilities of exosomes reflect the maturation signals received by DCs.
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PMID:ICAM-1 on exosomes from mature dendritic cells is critical for efficient naive T-cell priming. 1579 Jul 84

Recent data indicated that aging accelerated glomerular fibrin deposition induced by lipopolysaccharide (LPS) in mice. Our hypothesis was that aging may exacerbate glomerular inflammatory responses induced by glomerular fibrin deposition. Both young and aged rats with glomerular fibrin deposition induced by LPS were treated with tranexamic acid (TA) and TA plus urokinase (UK). Infiltrating inflammatory cells and expressions of monocyte chemoattractant protein 1, intercellular adhesion molecule 1, and vascular endothelial-cadherin were markedly upregulated in the LPS+TA group compared with the LPS group. Reduction of fibrin deposition in the LPS+TA+UK group was associated with downregulation of the above indices (p < .05), whereas the alteration of vascular endothelial-cadherin protein expression was negatively correlated with the fibrin deposition. There were also significant differences in increased expressions of monocyte chemoattractant protein 1 and intercellular adhesion molecule 1 between young and aged rats. These in vivo data demonstrated that fibrin deposition contributed to glomerular inflammatory responses, which could be exacerbated by aging.
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PMID:Effects of alterations of glomerular fibrin deposition on renal inflammation in rats at different age stages. 1618 47

The present study was undertaken to investigate the influence of insulin on lipopolysaccharide (LPS)-induced acute lung injury. Diabetic male Wistar rats (alloxan, 42 mg/kg, i.v., 30 days) and controls were instilled with saline containing LPS (750 microg/0.4 mL) or saline alone. The following analyses were performed 6 h there after: (a) total and differential cell counts in bronchoalveolar lavage (BAL) fluid, (b) quantification of tumor necrosis factor alpha, interleukin (IL) 1beta, IL-10, and cytokine-induced neutrophil chemoattractant 1 in the BAL (enzyme-linked immunosorbent assay), (c)immunohistochemistry for intercellular adhesion molecule 1 and E-selectin on lung vessels, and (d) quantification of metalloproteinases (MMP) 2 and 9 in the BAL (zymography). Relative to controls, diabetic rats exhibited a reduction in the number of neutrophils (80%) and reduced concentrations of tumor necrosis factor alpha (56%), IL-1beta (66%), and IL-10 (35%) after LPS instillation. Cytokine-induced neutrophil chemoattractant 1 levels did not differ between groups. Increased levels of MMP-2 (90%) and MMP-9 (500%) were observed in diabetic rats compared with controls. Treatment of diabetic rats with neutral protamine Hagedorn insulin (4 IU, s.c.), 2 h before LPS instillation, completely restored the number of neutrophils and concentrations of cytokines in the BAL fluid. Despite no significant differences between diabetic and control groups, there was a remarkable increase in intercellular adhesion molecule 1 and E-selectin expression on lung vessels after insulin treatment. Levels of MMP-2 and MMP-9 did not change after treatment with insulin. Levels of corticosterone were equivalent among groups. Data presented suggest that insulin modulates the production/release of cytokines and the expression of adhesion molecules controlling, therefore, neutrophil migration during the course of LPS-induced acute lung inflammation.
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PMID:Modulation of lipopolysaccharide-induced acute lung inflammation: Role of insulin. 1655 58

The lipopolysaccharide (LPS)-receptor complex, CD14/toll-like receptor 4, is known to play a role in the immune responses during sepsis. Excessive inflammation and tumor necrosis factor (TNF)-alpha synthesis have been reported to cause morbidity and mortality in endotoxemia and sepsis. Cell-to-cell interaction through the engagement between intercellular adhesion molecule 1, B7.1, and CD40 on monocytes and their ligands on T cells has been suggested to play a role in the inflammatory response such as TNF-alpha and interleukin 10 production. Nicotine, with the stimulation of the nicotinic acetylcholine receptor alpha7 subunit (alpha7-nAChR), has now become the focus of attention because of its anti-inflammatory effects. However, little is known about the mechanism of the inhibitory effects induced by nicotine on the LPS-induced immune responses. In the present study, we found that nicotine suppressed the expression of CD14, toll-like receptor 4, intercellular adhesion molecule 1, B7.1, and CD40 on monocytes and the production of TNF-alpha, but not interleukin 10, in human peripheral blood mononuclear cells in the presence of LPS. The actions of nicotine were reversed by a nonselective and a selective alpha7-nAChR antagonist, mecamylamine and alpha-bungarotoxin, respectively. Therefore, nicotine might inhibit the LPS receptor complex expression via alpha7-nAChR, thus leading to a decrease in the adhesion molecule expression and TNF-alpha production. Moreover, we demonstrated that a nuclear factor-kappaB and a p38 mitogen-activated protein kinase inhibitor mimicked the actions of nicotine in the presence of LPS. These results suggested that the nuclear factor-kappaB and p38 mitogen-activated protein kinase might be involved in the actions of nicotine.
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PMID:Stimulation of alpha7 nicotinic acetylcholine receptor inhibits CD14 and the toll-like receptor 4 expression in human monocytes. 1698 Aug 82

Inhaled lipopolysaccharide (LPS) induces an inflammatory response that may contribute to the pathogenesis of asthma and other airway diseases. Here we investigate the role of tumour necrosis factor (TNF) receptor-associated factor 1 (TRAF1) in leucocyte recruitment using a model of LPS-induced lung inflammation in mice. TRAF1(-/-) mice are completely deficient in the recruitment of lymphocytes to the lower respiratory tract after inhalation of LPS. Although TRAF1(-/-) mice display normal early accumulation of neutrophils, dendritic cells and monocytes in the alveolar airspace, they have a significantly reduced recruitment of these cells by 24 hr after inhalation of LPS when compared to wild-type (WT) mice. Despite normal expression of the pro-inflammatory cytokines TNF, interleukin-1 (IL-1) and IL-6 after LPS treatment, TRAF1(-/-) mice displayed decreased expression of intercellular adhesion molecule 1, vascular cell adhesion molecule 1, CCL17 and CCL20 in the lungs, when compared to LPS-treated WT mice. These results suggest that TRAF1 facilitates LPS-induced leucocyte recruitment into the lung airways by augmenting the expression of chemokines and adhesion molecules. Mice lacking TNF receptor 1 (TNFR1) but not TNFR2 show a phenotype similar to the TRAF1(-/-) mice, suggesting that TRAF1 may act downstream of TNFR1. Significantly, we use bone marrow chimeras to demonstrate that expression of TRAF1 by cells resident in the lungs, but not by circulating leucocytes, is necessary for efficient LPS-induced recruitment of leucocytes to the lung airways.
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PMID:TRAF1 regulates recruitment of lymphocytes and, to a lesser extent, neutrophils, myeloid dendritic cells and monocytes to the lung airways following lipopolysaccharide inhalation. 1732 85

Natural melanocortin peptides exert broad effects on the host and they have remarkable therapeutic potential. However, successful use of melanocortins as therapeutic agents depends on the design of molecules that have more stable pharmacological profiles. The synthetic peptide (CKPV)(2), based on the C-terminal sequence of alpha-melanocyte stimulating hormone (alpha-MSH), has anti-tumor necrosis factor-alpha (TNF-alpha) effects in vitro and in vivo and is a promising candidate to treat inflammation. Because neutrophil activity is a major target for anti-inflammatory therapies, we determined whether (CKPV)(2) modulates human neutrophil functions in vitro. Incubation of freshly-separated human neutrophils with 10(-12)-10(-6)M (CKPV)(2) significantly inhibited activities relevant to the inflammatory reaction. Neutrophil migration toward the two chemoattractants interleukin 8 (IL-8) and N-formyl-methionyl-leucyl-phenylalanine (fMLP) was significantly inhibited by (CKPV)(2). (CKPV)(2) also inhibited reactive oxygen intermediate (ROI) production induced by phorbol 12-myristate 13-acetate (PMA), but not that induced by fMLP. Because these effects of (CKPV)(2) were abolished by the adenylyl cyclase inhibitor 2',5'-dideoxyadenosine (ddAdo), they appear to be cAMP-dependent. Finally, the peptide reduced lipopolysaccharide (LPS)-stimulated expression of TNF-alpha, interleukin-1beta (IL-1beta), interleukin-8 (IL-8), and intercellular adhesion molecule 1 (ICAM-1), as well as TNF-alpha protein release in cell supernatants. The data indicate that (CKPV)(2) modulates broad cAMP-dependent, anti-inflammatory pathways in human neutrophils.
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PMID:The synthetic melanocortin (CKPV)2 exerts broad anti-inflammatory effects in human neutrophils. 1785 Sep 21

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