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)

A marked increase in adrenomedullin (AM) concentration was observed in rat plasma collected after intravenous infusion of lipopolysaccharide (LPS). Plasma immunoreactive (ir-) AM concentration increased already after 1 h exposure to 5 mg/kg of LPS and was elevated to 49.7 +/- 2.3 fmol/ml (mean +/- SEM) at 3 h after injection in contrast to 2.7 +/- 0.3 fmol/ml in saline-injected control rats. Plasma ir-AM level increased in a dose-dependent manner in a range of 0.008 to 5.0 mg/kg of LPS. AM gene transcription in LPS-injected rats was augmented more than 3-fold in ileum, liver, lung, aorta, and 2.4-fold even in skeletal muscle, in which AM was not thought to be produced in myocytes. These results, along with our recent data that AM production in cultured vascular smooth muscle cells (VSMCs) is stimulated with LPS, indicate that AM production is highly augmented in blood vessel, lung and intestine by administration of LPS. Since VSMCs express AM-specific receptors, secreted AM is deduced to actually exert a vasorelaxant effect especially in the endotoxin shock.
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PMID:Endotoxin markedly elevates plasma concentration and gene transcription of adrenomedullin in rat. 748 88

This study was undertaken to determine the effects of adrenomedullin (AM) on the secretion of cytokine-induced neutrophil chemoattractant (CINC), a member of the interleukin-8 family, from lipopolysaccharide-stimulated rat alveolar macrophages in vitro. AM significantly increased cAMP levels in alveolar macrophages in a dose-dependent fashion. On the other hand, AM significantly inhibited CINC secretion from alveolar macrophages in a dose-dependent fashion, and 8-bromo-cyclic adenosine monophosphate (8-Br-cAMP) also significantly inhibited CINC secretion. These findings suggest that AM may play important roles in the regulation of airway inflammation via a cAMP-dependent mechanism.
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PMID:Adrenomedullin inhibits the secretion of cytokine-induced neutrophil chemoattractant, a member of the interleukin-8 family, from rat alveolar macrophages. 759 89

To elucidate physiological functions of adrenomedullin (AM) secreted from vascular smooth muscle cells (VSMCs), we examined the effect of cytokines, growth factors and related substances on AM production in cultured rat VSMC. Among them, interleukin-1 alpha (IL-1 alpha), IL-1 beta, tumor necrosis factor-alpha (TNF-alpha) and TNF-beta, as well as lipopolysaccharide (LPS), markedly augmented production and gene expression of AM. Although maximal stimulation levels of these substances were not greatly different, ED50 values of IL-1s (0.3 ng/ml) were about 1/10 that of TNFs and LPS. AM mRNA levels maximized at 3-6 h after stimulation with IL-1 beta and LPS, while TNF-alpha increased the AM mRNA level up to 48 h. Furthermore, IL-1 alpha, TNF-alpha and LPS additively increased AM production in VSMC. AM production was slightly augmented by fibroblast, epidermal and platelet derived growth factors. These results suggest that AM secreted from VSMC actually exerts a vasorelaxant effect under physiological conditions such as endotoxin shock, atherosclerosis and inflammation.
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PMID:Interleukin-1, tumor necrosis factor and lipopolysaccharide additively stimulate production of adrenomedullin in vascular smooth muscle cells. 785 73

Wistar rats were injected intravenously with bacterial lipopolysaccharide (LPS) and developed endotoxic shock with severe hypotension. This was accompanied by significantly elevated concentrations of adrenomedullin (AM) in the plasma and expression of high levels of AM mRNA in the lung. Pretreatment of the rats with dexamethasone (DEX) prevented hypotension caused by LPS administration, but plasma AM concentrations and AM mRNA levels in the lung remained elevated. Adrenalectomized (ADX) rats developed a more severe form of circulatory shock in response to a low-dose of LPS. This was accompanied by only a slight increase in circulating AM in the plasma. However, pretreatment of ADX rats with DEX caused substantial elevations of plasma AM concentrations and expression of AM mRNA in the lung. Our studies demonstrate that glucocorticoid upregulates the expression and secretion of AM in vivo, and endogenous glucocorticoid is required for increased AM secretion under certain conditions such as endotoxic shock.
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PMID:Glucocorticoid regulation of adrenomedullin in a rat model of endotoxic shock. 951 4

In addition to endothelial cells and vascular smooth muscle cells, we demonstrated that adrenomedullin (AM) is synthesized and secreted from fibroblasts, Swiss 3T3, Hs68, and NHLF cells, in a native and biologically active form. Synthesis and secretion of AM from these fibroblasts was regulated by inflammatory cytokines, such as tumor necrosis factor and interleukin-1, lipopolysaccharide, growth and differentiation factors, and hormones in a manner similar to that of vascular smooth muscle cells and endothelial cells. Tumor necrosis factor-alpha, interleukin-1beta, and dexamethasone elevated AM secretion, whereas transforming growth factor-beta1 and interferon-gamma suppressed it in these three fibroblasts. Swiss 3T3 cells were shown to express receptors specific for AM by both cAMP production and receptor binding assay, and AM was found to stimulate DNA synthesis of quiescent cells through the cAMP-mediated pathway. AM secreted from Swiss 3T3 cells was also confirmed to augment cAMP production and DNA synthesis in the cells themselves. These effects were inhibited by a neutralizing monoclonal antibody against AM. These findings raise the possibility that AM functions as a growth regulator in the case of Swiss 3T3 cells. As AM receptors are widely distributed, AM secreted from fibroblast may play a role as a local regulator in mesenchymal cells of inflammatory or wounded regions.
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PMID:Adrenomedullin production in fibroblasts: its possible function as a growth regulator of Swiss 3T3 cells. 956 71

Septic shock is a life-threatening disorder caused by lipopolysaccharide (LPS) and other bacterial products. Accumulating evidence indicates a role for vasoactive substances and cytokines in this disease process. In this study we examined the effect of LPS on the gene expression of endothelin-1 (ET-1) and adrenomedullin (AM), two major vasoactive peptides predominantly produced by vascular endothelial cells, to investigate their role in the pathophysiology of septic shock. LPS induced ET-1 and AM gene expression in the heart, lung, kidney, liver, and aorta within 6 h. In the liver, whereas basal ET-1 and AM mRNA were hardly detectable, ET-1 and AM gene expression and peptide production were markedly increased by LPS. This LPS-induced upregulation of ET-1 and AM expression is greatly potentiated by D-galactosamine (D-GalN), although D-GalN alone could not induce ET-1 and AM gene expression. These results, together with the previous findings that liver injury induced by LPS and D-GalN is mainly mediated by tumor necrosis factor-alpha (TNF-alpha), suggest that the LPS-cytokine pathway may cause upregulation of ET-1 and AM production, leading to dysregulation of systemic and regional vascular tone.
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PMID:Upregulation of endothelin-1 and adrenomedullin gene expression in the mouse endotoxin shock model. 959 37

We demonstrated that adrenomedullin (AM) is produced and secreted from human leukemia cell lines (THP-1 and HL-60) as well as peripheral blood granulocytes, lymphocytes, monocytes and monocyte-derived macrophages. Immunoreactive AM accumulated in the culture media of THP-1 and HL-60 cells increased according to their differentiation into macrophage-like cells. Retinoic acid exerted synergistic effects on AM secretion from THP-1 and HL-60 cells when administered with tumor necrosis factor-alpha, lipopolysaccharide or 12-O-tetradecanoyl phorbol-13-acetate. AM was shown to increase the scavenger receptor activity on THP-1 cells. Thus, monocytes/macrophages should be recognized as sources of AM, and the secreted AM may modulate the function of macrophages.
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PMID:Adrenomedullin production is correlated with differentiation in human leukemia cell lines and peripheral blood monocytes. 959 15

We demonstrate that adrenomedullin (AM) is produced and secreted from cultured murine monocyte/macrophage cell line (RAW 264.7) as well as mouse peritoneal macrophage. Immunoreactive (IR) AM secreted from RAW 264.7 cells was chromatographically identified to be native AM. To elucidate the regulation mechanism of AM production in macrophage, we examined the effects of various substances inducing differentiation or activation of monocyte/macrophage. Phorbol ester (TPA), retinoic acid (RA), lipopolysaccharide (LPS), and interferon-gamma (IFN-gamma) increased AM production 1.5-7-fold in RAW 264.7 cells in a dose- as well as time-dependent manner. By LPS stimulation, the AM mRNA level in RAW 264.7 cells was augmented up to 7-fold after 14 h incubation. RA exerted a synergistic effect when administered with TPA, LPS, or IFN-gamma, whereas IFN-gamma completely suppressed AM production in RAW 264.7 cells stimulated with LPS. Dexamethasone, hydrocortisone, estradiol, and transforming growth factor-beta dose-dependently suppressed AM production in RAW 264.7 cells. AM production was also investigated in mouse peritoneal macrophage. Primary mouse macrophage secreted IR-AM at a rate similar to that of RAW 264.7 cells, and its production was enhanced 9-fold by LPS stimulation. AM was found to increase basal secretion of tumor necrosis factor alpha (TNF-alpha) from RAW 264.7 cells, whereas AM suppressed the secretion of TNF-alpha and interleukin-6 from that stimulated with LPS. Thus, macrophage should be recognized as one of the major sources of AM circulating in the blood. Especially in cases of sepsis and inflammation, AM production in macrophage is augmented, and the secreted AM is deduced to function as a modulator of cytokine production.
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PMID:Production of adrenomedullin in macrophage cell line and peritoneal macrophage. 964 28

In this study, we examined urinary levels of adrenomedullin (AM) in 18 healthy volunteers and 18 patients with cystitis. We also compared urinary levels of AM in 11 patients with cystitis before and after antibiotic treatment. Urinary AM concentrations were measured by a radioimmunoassay specific for human AM. Urinary AM levels in patients with cystitis were significantly elevated compared with those of healthy volunteers and correlated positively with the number of urine leukocytes. By antibiotic treatment, urinary AM levels significantly decreased as compared with before the treatment. By RNA blot analysis of AM transcript, we detected significant levels of AM mRNA in canine urinary bladder and ureter. Intravenous administration of lipopolysaccharide elevated the AM mRNA level in the urinary bladder. These data suggest that infection and inflammation stimulate AM production in the urinary tract, which results in increased urinary AM levels in patients with cystitis. Based on these results, it is deduced that AM participates in the pathophysiology of cystitis, and its urinary level could be used as an index of the degree of cystitis.
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PMID:Increased urinary levels of adrenomedullin in patients with cystitis. 1019 22

1. The functional involvement of the vasodilator peptides, adrenomedullin (ADM) and calcitonin gene-related peptide (CGRP), in the haemodynamic sequelae of continuous infusion of lipopolysaccharide (LPS) was assessed in conscious, male, Long Evans rats, by the use of peptide antagonists. 2. It was demonstrated that ADM (22-52) at a dose of 500 nmol kg-1 h-1 caused significant inhibition of the effects of ADM (1 nmol kg-1), without affecting responses to CGRP (0.1 or 1 nmol kg-1). 3. Even when the regional vasodilator responses to LPS infusion were enhanced (by pre-treatment with dexamethasone and the endothelin antagonist, SB 209670, or by pretreatment with SB 209670 and the AT1-receptor antagonist, losartan), ADM (22-52) had no significant cardiovascular effects. In contrast, the CGRP1-receptor antagonist, CGRP (8-37), caused small, but significant, inhibitions of the hypotensive and renal and mesenteric vasodilator effects of LPS, but only 6 h after onset of infusion in the presence of dexamethasone and SB 209670. 4. The results indicate that, in this model of endotoxaemia, the marked regional vasodilatations seen in the presence of dexamethasone and SB 209670 do not involve ADM, but do involve CGRP, albeit only to a small extent.
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PMID:Influence of CGRP (8-37), but not adrenomedullin (22-52), on the haemodynamic responses to lipopolysaccharide in conscious rats. 1045 17


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