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)

Mice were injected with Corynebacterium parvum, which induces multiple granulomas in liver and renders animals hyper-reactive to the lethal effect of bacterial lipopolysaccharide (LPS). Such animals when challenged with LPS developed also extensive liver parenchymal cell damage as estimated by elevated blood asparate transaminase levels and a hypoglycaemia. Treatment with indomethacin, hydrocortisone, dexamethasone, promethazine, metiazinic acid and (+)-catechin ameliorated the liver damage. Hydrocortisone, dexamethasone, promethazine and metiazinic acid also reduced the mortality rate in mice challenged with LPS. Diarrhoea, accompanying the LPS-induced shock, was prevented by the drugs used. Possible agents mediating the hepatotoxic and shock effects of LPS are discussed.
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PMID:Protection of mice against endotoxin-induced liver damage by anti-inflammatory drugs. 54 79

Tumor necrosis factor (TNF), interleukin 1 (IL-1) and interleukin 6 (IL-6) are central mediators of the inflammatory response. We investigated the modulation of these cytokines by hormones in vitro. Murine adherent peritoneal exudate cells (PEC) were exposed to various concentrations of hormones followed by lipopolysaccharide (LPS, 10 micrograms/ml). TNF, IL-1 and IL-6 production were assessed by bioassays, enzyme-linked immunosorbent assays (ELISA) or Western blot, and specific RNA transcripts by Northern blot. Hydrocortisone in concentrations as low as 10 ng/ml had dramatic inhibitory effects on supernatant levels of TNF and IL-1 and on TNF, IL-1 and IL-6 transcript number. Supernatant levels of IL-6 were only slightly diminished by hydrocortisone. Adrenocorticotrophic hormone (ACTH) and insulin increased supernatant levels of TNF bioactivity in response to LPS, while each decreased available TNF-alpha gene transcripts. Thus TNF protein production was affected at a post-transcriptional level. ACTH and insulin increased supernatant levels of IL-6 produced in response to LPS without altering available transcripts. Corticotrophin-releasing factor (CRF), epinephrine and glucagon had no effect on supernatant levels of cytokine. Thus, physiological and pharmacological concentrations of hydrocortisone had dramatic inhibitory effects on the supernatant levels of TNF and IL-1, and on the number of available TNF, IL-1 and IL-6 transcripts in PEC exposed to LPS, but had minimal effects on supernatant levels of IL-6 bioactivity. This hydrocortisone action may be a specific negative feedback system for IL-1 and TNF, with relative sparing of IL-6.
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PMID:Hormonal regulation of inflammatory cell cytokine transcript and bioactivity production in response to endotoxin. 131 63

Inflammatory mediators, such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF alpha) are secreted by fixed tissue macrophages and exhibit local autocrine and paracrine effects as well as distant endocrine effects. Human fetal Kupffer cells, the fixed tissue macrophages of the liver, may play a role as modulators of immune and endocrine function in early embryonic and fetal development. In the present study we isolated human fetal Kupffer cells to greater than 90% purity and prepared short term cultures to investigate the effect of glucocorticoids on the secretion of the cytokine TNF alpha. Fetal Kupffer cells secreted TNF alpha and IL-1 beta after culture with bacterial lipopolysaccharide (LPS), indicating that these cells express mature macrophage function. Cortisol and dexamethasone dramatically suppressed the LPS-stimulated secretion of TNF alpha by fetal Kupffer cells. The inhibitory effects of glucocorticoids appeared to be specific, since estrogen, progesterone, and testosterone had no effect on LPS stimulation of TNF alpha production. None of the steroids tested altered basal production or enhanced the LPS-stimulated production of TNF alpha by fetal Kupffer cells. The inhibition by glucocorticoids could be reversed by the addition of RU 486, indicating that this effect was mediated by the glucocorticoid receptor. These results demonstrate that human fetal macrophages demonstrate mature macrophage function in early gestation; they can be activated to produce TNF alpha by a well characterized modulator of cellular function (LPS) and suppressed by glucocorticoids.
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PMID:Glucocorticoids inhibit lipopolysaccharide-induced production of tumor necrosis factor-alpha by human fetal Kupffer cells. 185 61

Inflammatory mediators such as interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) exhibit local autocrine and paracrine effects as well as distant systemic effects on target cells. Human Kupffer cells, the fixed tissue macrophages of the liver, may modulate immune and endocrine function in early fetal development. We purified and cultured human fetal Kupffer cells to investigate the production of the cytokine, IL-6. Fetal Kupffer cells treated with bacterial lipopolysaccharide (LPS) produced IL-6 in a dose-dependent fashion with maximal secretion (1000 pg per 10(6) cells) observed within 12 h using 10 micrograms of LPS/ml. Cortisol and dexamethasone, but not oestrogen, progesterone, or testosterone, dramatically suppressed the LPS-stimulated secretion of IL-6 by fetal Kupffer cells. None of the steroids tested altered basal production or enhanced the LPS-stimulated production of IL-6 by fetal Kupffer cells. The inhibition of glucocorticoids could be reversed by the addition of RU 486, indicating that this effect was mediated by the glucocorticoid receptor. These results demonstrate that the production of IL-6 by fetal hepatic macrophages can be activated by LPS and suppressed by glucocorticoids. These studies suggest that Kupffer cells express mature macrophage function in early gestation and would be capable of regulatory roles in the growth and development of the fetus.
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PMID:Regulation of interleukin-6 production in human fetal Kupffer cells. 203 Nov 50

We have examined the effect of dexamethasone (DM) and cortisol on the production of interleukin (IL)6 from the murine macrophage cell line RAW264.9, human monocytes, human endothelial cells and the human fibroblast cell line FS4. In RAW264.9 cells DM in the concentration range 10(-9) M to 10(-6) M inhibited the lipopolysaccharide (LPS)-induced production of IL6 by 10% to 90%. Cortisol had a similar effect, but was about 25 times less potent than DM. Also, when 10(-6) M of DM was added to the cultures after addition of LPS, it completely inhibited the residual 24-h production of IL6. Corresponding to the effect on IL6 production, DM (10(-6) M) reduced the mRNA levels for IL6 in the RAW264.9 cells. The glucocorticoid analogue RU 486 competes with DM and cortisol for the glucocorticoid receptor and reversed the inhibitory effect of DM, demonstrating that DM exerts its effect via the glucocorticoid receptor. DM also had an inhibitory effect on LPS-stimulated IL6 production in freshly isolated human monocytes, and on IL 1-stimulated IL6 production in human endothelial cells and FS4 fibroblasts. These results demonstrate that DM via a receptor-mediated mechanism inhibits IL6 production at the transcriptional level, and this may contribute to the anti-inflammatory and immunosuppressive effect of glucocorticoids.
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PMID:Glucocorticoids inhibit the production of IL6 from monocytes, endothelial cells and fibroblasts. 225 84

Effects of E-5110, a novel non-steroidal antiinflammatory drug, on interleukin-1 (IL-1) generation from human monocytes were studied in vitro. E-5110 reduced the amounts of extra- and intracellular IL-1 activity induced by lipopolysaccharide (LPS, 1 micrograms/ml) in a dose-dependent manner (1-10 microM). E-5110 also inhibited the IL-1 generation induced by antigen-antibody complexes, opsonized zymosan and silica particles. It was suggested that the inhibition of IL-1 generation by E-5110 was independent of the inhibitory effects on arachidonate cyclooxygenase and/or lipoxygenase because indomethacin, piroxicam, BW755C and AA861 had no effects on IL-1 generation. Hydrocortisone (IC50:0.084 microM), aurothioglucose (11.5 microM) and lobenzarit (75.0 microM), which are clinically effective antirheumatic drugs, also inhibited IL-1 generation, like E-5110 (1.21 microM). It is expected that E-5110 will be superior to classical non-steroidal antiinflammatory drugs in medical treatment of rheumatoid arthritis.
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PMID:Inhibitory effects of E-5110 on interleukin-1 generation from human monocytes. 280 17

The combined effect of hydrocortisone (HC) and interferon-gamma and -alpha (IFN-gamma and -alpha) on human blood monocytes (Mo) interleukin 1 (IL 1) secretion was investigated. IL 1 was generated by treating the fresh or aged Mo with lipopolysaccharide (LPS), and quantitated by radioimmunoassay (RIA). Hydrocortisone, at the pharmacological attainable concentration of 10(-5) molar (M), markedly suppressed fresh Mo IL 1 secretion but had no effect at lower tested doses. Addition of IFN-gamma enhanced the IL 1 secretion of fresh Mo; however, the simultaneous addition of 10(-5) M HC and IFN-gamma resulted in marked suppression of the monokine release. Monocytes, when cultured in vitro for three days, lost the capacity to secrete IL 1. The loss of IL 1 secretory potential of aged Mo was prevented by preincubating them with IFN-gamma prior to LPS stimulation. IFN-alpha was ineffective in this regard. Aged Mo, pretreated with the combination of IFN-gamma and HC were still able to secrete abundant quantities of IL 1, demonstrating the failure of HC to suppress the IFN-gamma-induced augmentation of IL 1 secretory potential. Even suprapharmacologic doses of HC (10(-4) M) did not inhibit this enhancement and actually further augmented it. Thus, therapeutic concentrations of HC suppress IL 1 secretion of fresh Mo even in the presence of IFN-gamma; however, therapeutic or suprapharmacologic concentrations of HC do not inhibit the IL 1 secretory capacity of IFN-gamma-treated aged Mo.
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PMID:Failure of hydrocortisone to suppress the interferon-gamma-induced augmentation of interleukin 1 secretion of aged human monocytes. 313 48

Pro-inflammatory cytokines mediate their biological functions after they are secreted or released from intracellular to extracellular milieu. Keratinocytes have proven to be able to produce various cytokines including IL-1 and IL-8. Dysregulations of IL-1 and IL-8 were found in psoriatic lesions. Recently, vitamin D3 (VD3) was found to be an effective and safe therapy for psoriasis. In the present study, we investigated the effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and its analogue MC903 on IL-1 alpha and IL-8 secretion by human keratinocytes in vitro. Cultured normal human keratinocytes (NHKs) produced considerable amounts of IL-1 alpha but secreted less. In contrast, they produced less IL-8 and almost all molecules were secreted to the culture supernatants. Treatment of unstimulated NHKs with 1,25(OH)2D3 or MC903 showed little effects on IL-1 alpha production and secretion though they slightly enhanced IL-8. When NHKs were stimulated with tumour necrosis factor-alpha (TNF alpha), both IL-1 alpha and IL-8 secretions were enhanced and these enhancements were inhibited by 1,25(OH)2D3 or MC903. Stimulation of NHKs with phorbol 12-myristate 13-acetate(PMA) and lipopolysaccharide(LPS) resulted in an increase of IL-8 and decrease of IL-1 alpha in the culture supernatants. Addition of 1,25(OH)2D3 or MC903 inhibited the increased secretion of IL-8 but restored decreased secretion of IL-1 alpha from stimulated NHKs dose dependently. Hydrocortisone and cyclosporin A showed similar inhibitory effects on PMA/LPS-increased IL-8 secretion from NHKs but had little effect of restoring IL-1 alpha.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulatory effects of 1,25-dihydroxyvitamin D3 and a novel vitamin D3 analogue MC903 on secretion of interleukin-1 alpha (IL-1 alpha) and IL-8 by normal human keratinocytes and a human squamous cell carcinoma cell line (HSC-1). 819 81

Production of interleukin 6 (IL-6) from cultured human retinal pigment epithelial cells (RPE) was demonstrated using an enzyme-linked immunosorbent assay. Production of IL-6 occurred without any stimulation and significantly increased approximately 2-5 times by lipopolysaccharide (LPS) or interleukin 1 alpha stimulation. Hydrocortisone reduced the production of the LPS-stimulated IL-6 to a half level. Both gel filtration and western blotting analysis indicated the molecular weight of IL-6 as 30,000-35,000. IL-6 produced in the RPE may play a role in amplifying ocular immune and inflammatory responses.
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PMID:[Human cultured retinal pigment epithelial cells produce interleukin-6]. 843 35

Tumor necrosis factor-alpha (TNFalpha) is an important mediator in bacterial lipopolysaccharide (LPS)-induced fever and shock. New data on TNFalpha-producing macrophages in heart, pituitary gland, kidneys and liver in correlation with TNFalpha plasma levels are reported here. In adult rabbits, core temperature and TNFalpha plasma levels are significantly increased at 3 and 24 h after treatment with LPS. After a delay of 6-12 h, the number of TNFalpha-containing macrophages, determined by immunohistochemistry, increases more than fivefold in all organs investigated. With the exception of the pituitary gland, the increase in cell number is correlated with the degree of cellular injury, indicating the involvement of TNFalpha in LPS-induced organ damage that is accompanied by the synthesis of the cytokine. Cortisol levels also increase for at least 24 h after LPS treatment, show peak values 6 h after interleukin-1 treatment, and are unchanged after TNFalpha treatment, indicating the different effects of these factors on the hypothalamo-hypophyseal-adrenocortical axis. This study provides evidence that macrophageal TNFalpha of multi-organ origin is involved in LPS-induced tissue injury and supports the concept of a systemic inflammatory response syndrome. We also show for the first time that in the anterior lobe of the pituitary gland TNFalpha is a normal constituent in cells producing growth hormone but not ACTH. Moreover, most cells of the intermediate lobe are positive for TNFalpha.
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PMID:Tumor necrosis factor-alpha in macrophages of heart, liver, kidney, and in the pituitary gland. 876 56


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