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)

To determine whether endotoxemia and release of tumor necrosis factor (TNF-alpha) and/or interleukin 1 alpha (IL-1 alpha) are involved in the pathogenesis of heatstroke, 17 adult patients with a mean rectal temperature of 42.1 +/- 0.2 degrees C were studied. Blood samples were taken on admission and after cooling was completed. TNF-alpha and IL-1 alpha levels were measured by enzyme-linked immunosorbent assay, and lipopolysaccharide (LPS) content was measured by the chromogenic substrate modification of the Limulus amebocyte lysate. TNF-alpha, IL-1 alpha, and LPS were elevated in all patients [199 +/- 25 (SE) pg/ml, 480.5 +/- 68.3 pg/ml, and 8.60 +/- 1.19 ng/ml, respectively, compared with normal control values of 31.4 +/- 8.4 pg/ml, 53.7 +/- 5.32 pg/ml, and less than 9 pg/ml]. There was no significant correlation between temperature and the circulating concentration of TNF-alpha, IL-1 alpha, and LPS. Postcooling TNF-alpha, IL-1 alpha, and LPS concentrations were significantly decreased but still above normal control values. The findings suggest that these mediators may have a role in the pathogenesis of heatstroke that could change the strategy of management.
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PMID:Endotoxemia and release of tumor necrosis factor and interleukin 1 alpha in acute heatstroke. 188 59

The cytokine neutrophil-activating peptide-1/interleukin-8 (NAP/IL-8) activates neutrophils (PMN) and elicits selective diapedesis of PMN into the extracellular space. The glomerular mesangial cell (MC) is a specialized pericyte that controls glomerular filtration and synthesizes and responds to a variety of cytokines. Because of its location within the glomerulus, the MC is in a pivotal position to orchestrate events underlying immune injury. Since immune-injured glomeruli have been shown to produce NAP/IL-8 activity in vitro, we assessed whether lipopolysaccharide (LPS)- or cytokine-activated MC might be a source of this activity. Pure human MC, devoid of monocyte/macrophage and fibroblast contamination, were grown by explant from collagenase-treated glomeruli. Human recombinant interleukin-1 alpha (IL-1 alpha, 20 ng/ml), IL-1 beta (50 ng/ml), tumor necrosis factor alpha (TNF, 100 ng/ml) and lipopolysaccharide (LPS, 10 micrograms/ml) stimulated release of a neutrophil chemotactic factor from cultured MC. Both concentrated (fivefold) and unconcentrated MC supernatants stimulated directed neutrophil migration under agarose at a level similar to that of the bacterial chemotactic factor, FMLP. In contrast, unstimulated MC-conditioned media and IL-1 alpha, IL-1 beta. TNF and LPS in medium alone did not directly induce PMN migration. Molecular sizing studies using sequential membrane ultrafiltration identified significant TNF-stimulated, MC-derived chemotactic activity in the 3000 to 10000 kD fraction. An anti-NAP/IL-8 monoclonal antibody, 46E5, significantly inhibited PMN chemotaxis stimulated by TNF-stimulated, MC-conditioned media in a dose-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytokine- and LPS-induced synthesis of interleukin-8 from human mesangial cells. 189 76

Interactions between leukocytes and endothelial cells, particularly in the microvasculature, are important for the initiation and regulation of tissue inflammation. These interactions are regulated by the recognition of specific cell adhesion molecules (CAM) on both leukocytes and endothelial cells. In this study, we examined the modulation of cell surface expression of MHC antigens and the CAM intercellular adhesion molecule 1 (ICAM-1), lymphocyte function antigen 3 (LFA-3), and CD44 on human dermal microvascular endothelial cells (HDMEC) both grown in monolayers and differentiated into capillary-like structures on the basement membrane-like substrate matrigel. HDMEC grown in monolayers or differentiated on matrigel express comparable cell surface MHC class I, LFA-3, CD44, and ICAM-1. ICAM-1, but not LFA-3 or CD44, was increased in expression in a dose- and time-dependent manner by interleukin 1 (IL-1) alpha, tumor necrosis factor (TNF) alpha, lipopolysaccharide (LPS), or interferon (IFN) gamma. Comparable upregulation was observed both in cells grown in monolayers and cells differentiated on matrigel. IL-1 alpha, TNF alpha, and LPS increased ICAM-1 expression on average 100-200% whereas IFN gamma was somewhat less potent. Comparative studies with human umbilical vein endothelial cells (HUVEC) demonstrated consistently lower levels of ICAM-1 expression on HUVEC, but greater increases after cytokine stimulation. Pretreatment with dexamethasone or transforming growth factor (TGF) beta did not affect baseline expression of ICAM-1 or inhibit upregulation of ICAM-1 on HDMEC by IL-1 alpha, TNF alpha, LPS, or IFN gamma. Both IFN gamma and TNF alpha, but not IL-1 alpha increased MHC class I expression, whereas only IFN gamma induced the expression of HLA-DR on HDMEC. The effect of IL-1 alpha, TNF alpha, or IFN gamma was inhibited by antibody to the specific cytokine, but was unaffected by antibody to other cytokines. Additionally, IFN alpha or beta inhibited upregulation of HLA-DR by IFN gamma, but had no effect on the increased MHC class I or ICAM-1 expression mediated by this cytokine. These data demonstrate that the expression of CAM and MHC antigens on small vessel-derived endothelial cells is different from that observed on large-vessel HUVEC, is regulated by the presence of multiple cytokines operating via distinct pathways, and the expression and regulation of these proteins appear to be similar on cells that have been grown in monolayers to those morphologically differentiated into blood vessel-like structures.
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PMID:Studies of the modulation of MHC antigen and cell adhesion molecule expression on human dermal microvascular endothelial cells. 190 7

The present study was designed to examine the effect of physical exercise on production of interleukin-1 (IL-1), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2) and interferon-gamma (IFN-gamma). Ten young, healthy volunteers underwent 60-min bicycle exercise at 75% of maximal oxygen uptake (VO2max). Blood samples were collected before and during the last minutes of exercise, as well as 2 h and 24 h later. Blood mononuclear cells (BMNC) were stimulated in vitro with either bacterial lipopolysaccharide or phytohaemagglutinin, and the supernatants were tested for the above-mentioned cytokines using bioassays as well as ELISA techniques. The production of IL-6 increased significantly 2 h after exercise, furthermore the production of IL-1 alpha and IL-1 beta was enhanced, although only borderline significant. TNF-alpha, IL-2 and IFN-gamma did not fluctuate in relation to exercise. The increased amounts of IL-1 and IL-6 in the supernatants generated from a fixed number of BMNC are most likely explained by the increased percentage and absolute number of blood monocytes 2 h after exercise. IL-2 and IFN-gamma are mainly produced by CD4+ and CD16+ cells. During exercise the CD4+ subset decreases, while the CD16+ subset increases. The finding of unchanged production of IL-2 and IFN-gamma was therefore expected.
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PMID:Effect of physical exercise on in vitro production of interleukin 1, interleukin 6, tumour necrosis factor-alpha, interleukin 2 and interferon-gamma. 190 58

The amplification of cytokine mRNA following incubation of macrophages with inflammatory stimuli and protein synthesis inhibitors has been related to stabilization of labile mRNA species containing the 3'AUUUA consensus sequence. In the present study, cycloheximide-treated lipopolysaccharide (LPS)-stimulated murine peritoneal macrophages had a five- to six-fold increase in tumour necrosis factor (TNF) mRNA when compared to parallel LPS-stimulated controls. Interleukin-1 beta (IL-1 beta) mRNA levels in these cells, however, were significantly lower than the LPS controls. The down-regulation of IL-1 beta by cycloheximide was not apparent for IL-1 alpha mRNA, which had a two- to three-fold increase in the LPS-stimulated cycloheximide-treated macrophages. A similar profile was observed in vivo in which up-regulation of TNF, but not IL-1 beta mRNA, was apparent in mice administered cycloheximide plus LPS relative to LPS alone. Cycloheximide-treated LPS-stimulated macrophages demonstrated a significant increase in transcriptional activity for TNF, but not IL-1 beta, by nuclear run-on transcription assays and an increase in the amount of the nuclear binding factor NFKB when compared to LPS controls. The cycloheximide-mediated increase in TNF mRNA was also related to an increased stability of the TNF message, while no significant increase in stability was apparent in IL-1 beta mRNA. Therefore, the differential expression of TNF and IL-1 beta mRNA in cycloheximide-treated macrophages involves both transcriptional and post-transcriptional regulatory mechanisms.
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PMID:Transcriptional and post-transcriptional mechanisms involved in the differential expression of LPS-induced IL-1 and TNF mRNA. 191 97

Previously we described a cell line OCI-LY3 derived from a patient with non-Hodgkin's lymphoma. The cell line produced interleukin-6 (IL-6) mRNA and protein and demonstrated an autocrine pattern of growth for IL-6. Southern blot analysis of the IL-6 gene did not reveal any rearrangement. To determine whether the production of IL-6 by OCI-LY3 was due to subtle changes in the promoter of IL-6 or due to the expression of trans-acting factors chloramphenicol acetyltransferase (CAT) reporter constructs containing from -1,180 to +13 to -112 to +13 of a normal IL-6 gene were electroporated into the cell line. When these constructs are transferred into unstimulated fibroblasts, no CAT activity is seen; however, CAT activity is induced when the cells are stimulated with either IL-1 alpha, lipopolysaccharide (LPS), or cyclic adenosine monophosphate (cAMP) analogues. When the cell line OCI-LY3 was transfected with these constructs, CAT activity was observed; it was not necessary to stimulate the cells with exogenous factors to observe this activity. No CAT activity was observed in a second lymphoma cell line, OCI-LY13.1, that does not produce IL-6. These results suggest that the constitutive production of IL-6 by the cell line OCI-LY3 is due to the presence of trans-acting factors that stimulate the expression of IL-6 and not due to a cis-acting mutation of the IL-6 promoter.
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PMID:Regulation of interleukin-6 expression in the lymphoma cell line OCI-LY3. 191 71

Human mesangial cells (MC) in culture, when stimulated by interleukin 1 alpha(IL-1 alpha) or tumour necrosis factor (TNF alpha), but not with lipopolysaccharide (LPS), express interleukin 8 (IL-8) mRNA, and both cell associated and extracellular IL-8. Dexamethasone treatment of mesangial cells induced partial inhibition of the release of extracellular IL-8, while cell-associated IL-8 and IL-8 mRNA were not significantly altered. We propose that the mesangial cell has a direct role in the initiation and propagation of inflammatory events within the glomerulus via the generation of the chemotactic cytokine IL-8.
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PMID:Cytokine-activated human mesangial cells generate the neutrophil chemoattractant, interleukin 8. 192 Nov 60

By using enzyme-linked immunosorbent assay (ELISA), it was demonstrated that cultured human corneal epithelial cells produced interleukin-6 (IL-6) without any stimulation. As lipopolysaccharide (LPS)-stimulation did not induce further production of IL-6 and IL-1 alpha, it was suggested that IL-6 was produced naturally as in the case of IL-1 alpha production which has been previously reported by the author. Production of IL-1 alpha and IL-6 in the human corneal epithelial cells may play a role in amplifying immune responses on the ocular surface.
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PMID:[Production of IL-6 and IL-1 alpha by human corneal epithelial cells]. 195 Aug 28

Bacteroides gingivalis (B. gingivalis) is isolated frequently from subgingival plaques of adult periodontal patients. B. gingivalis is a gram-negative anaerobic organism which has fimbriae on its cell surface. In the present study, B. gingivalis fimbriae were examined for their ability to adhere to human gingival fibroblasts (Gin-1), and to stimulate fibroblast-derived thymocyte-activating factor (FTAF) production by Gin-1 cells. The ability of the fimbriae to bind specifically to Gin-1 cells was clearly shown by competition assay between 125I-labeled and unlabeled fimbriae. Significant stimulatory effect of the fimbriae on FTAF production was observed, when the fimbriae were added to Gin-1 cells at a dose of 1 microgram/ml, and this stimulation was observed as early as 24 hr after addition of fimbriae to the cells. It was verified by a spleen cell mitogenic assay for the fimbriae that the stimulatory effect was not due to lipopolysaccharide (LPS) contamination of the fimbriae preparation. The FTAF activity was inhibited about 50% by recombinant human interleukin-1 (IL-1) beta antiserum but not by recombinant human IL-1 alpha antiserum. Therefore, the present study suggests that B. gingivalis fimbriae may play a functional role in the pathogenesis of adult periodontal disease induced by the microorganism.
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PMID:[Stimulatory effects of Bacteroides gingivalis fimbriae on production of fibroblasts-derived thymocyte-activating factor (FTAF) by human gingival fibroblasts]. 198 5

The macrophage-derived cytokines interleukin 1 alpha (IL-1 alpha) and tumor necrosis factor-alpha (TNF-alpha) have significant effects on hematopoiesis in vitro and in vivo. Studies in our laboratory have demonstrated that, in vivo, IL-1 alpha and TNF-alpha suppress late stage erythropoiesis while stimulating the macrophage-granulocyte lineage. In the present studies, we have examined the mechanisms of these effects. Normal mice were treated with a single dose of either recombinant murine IL-1 alpha or TNF-alpha (1.25 x 10(6) or 10(5) U/mouse i.p., respectively) with or without pretreatment of the animals with monoclonal anti-murine TNF-alpha antibody at a dose that has been shown to be capable of abrogating endogenous TNF activity induced by lipopolysaccharide (LPS). After 5 days, effects on late-stage erythropoiesis and macrophage formation were measured by determining the number of their progenitors, erythroid colony-forming units (CFU-E) and macrophage colony-forming units (CFU-M), in the spleen. Anti-TNF-alpha antibody treatment significantly abrogated CFU-E suppression by IL-1 alpha but had no effect on the IL-1 alpha-induced stimulation of CFU-M. IL-1 alpha and TNF-alpha suppressed CFU-E in vivo and stimulated CFU-M in the spleens of T-cell- and natural killer (NK)-cell-deficient mice. Neither cytokine suppressed CFU-E colony formation in vitro. These results demonstrate that IL-1 alpha-induced suppression of CFU-E is mediated through induction of TNF-alpha, IL-1 alpha stimulation of CFU-M was independent of TNF-alpha, and the in vivo hematopoietic effects of these cytokines do not strictly require intact T- and NK-cell function for activity.
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PMID:Negative regulators of in vivo erythropoiesis: interaction of IL-1 alpha and TNF-alpha and the lack of a strict requirement for T or NK cells for their activity. 199 91


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