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)

Prointerleukin 1 beta (IL-1 beta) is a cytokine that mediates a broad range of biological activities. Genomic sequences that regulate IL-1 beta transcription include both inducible regulatory elements located more than 2,700 bp upstream of the transcriptional start site (cap site) and proximal elements located near the TATA box of this gene. In this study, we focused on the identification and characterization of trans-acting nuclear regulatory proteins that bind to the cap site-proximal region of the human IL-1 beta gene. We identified a protein, termed NFIL-1 beta A (NF beta A), that binds to a highly conserved 12-bp DNA sequence (-49 to -38) located upstream of the TATA box motif in both the human and murine IL-1 beta genes. The IL-1 alpha gene, which lacks a TATA motif, does not possess an NF beta A-binding sequence within the promoter region, suggesting that NF beta A may selectively regulate IL-1 beta expression. Using electrophoretic mobility shift assays, we identified several distinct DNA-protein complexes that are expressed in a cell-type-specific manner. In monocytic cell lines, the relative abundance of these complexes varies rapidly following stimulation of the cells with phorbol esters or lipopolysaccharide. UV cross-linking analysis identified two distinct DNA-binding polypeptides that comprise distinct complexes. The functional role of NF beta A was assessed in transient transfection assays. These data indicate that NF beta A is required for both basal and inducible promoter activity in monocytic cells. Furthermore, the human cytomegalovirus immediate-early 1 gene product requires the presence of NF beta A in order to trans-activate the proximal IL-1 beta promoter in a monocytic cell line. We propose that NF beta A is a factor that mediates either direct or indirect activation by the immediate-early 1 gene product. The proximity of this essential factor to the TATA motif suggests a possible role in transcriptional initiation.
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PMID:The functional importance of a cap site-proximal region of the human prointerleukin 1 beta gene is defined by viral protein trans-activation. 163 Apr 55

Pseudomonas aeruginosa is a dominant pathogen in infection in cystic fibrosis. This bacterium is thought to play a major role in the chronic bronchial infection-induced pathophysiology. Our data showed that whole formalin-fixed heat-killed P. aeruginosa was mitogenic for human lymphocytes and induced production of substantial amounts of tumor necrosis factor alpha (TNF) in peripheral blood mononuclear leukocytes in cultures. Significant amounts of TNF were produced at 10(3) bacteria per 2 x 10(5) mononuclear leukocytes. Treatment of P. aeruginosa with polymixin B did not affect its ability to stimulate TNF production, suggesting that bacterial lipopolysaccharide is not involved. P. aeruginosa, however, did not stimulate production of the T-cell lymphokine lymphotoxin (TNF beta). Exotoxin A, considered to be an important virulence factor produced by P. aeruginosa, did not stimulate either lymphoproliferation or production of TNF. In fact, this toxin, at nontoxic concentrations, was found to depress lymphoproliferation induced by phytohemagglutinin and Staphylococcus aureus and decreased production of TNF, lymphotoxin, and gamma interferon in either lymphocytes or macrophages. This toxin similarly inhibited the production of interleukin-1 beta (IL-1 beta) and IL-1 alpha, but for the inhibition of the latter, 25-fold-less toxin was required than for inhibition of the former. Inhibition of production of TNF was as sensitive as the IL-1 alpha to exotoxin A. The effects of exotoxin A on lymphoproliferation and cytokine production could be neutralized by the addition of anti-exotoxin A antibodies. These results suggest that two mechanisms by which P. aeruginosa could contribute to the chronic bronchial infection-induced pathophysiology are the nonspecific stimulation of TNF and IL-1 and the release of exotoxin A, a toxin which depresses immune responses.
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PMID:Induction of tumor necrosis factor (TNF) and interleukin-1 (IL-1) by Pseudomonas aeruginosa and exotoxin A-induced suppression of lymphoproliferation and TNF, lymphotoxin, gamma interferon, and IL-1 production in human leukocytes. 163 87

Interleukin-1-like immunoreactivity has earlier been demonstrated by immunohistochemistry in the noradrenaline-containing chromaffin cells of the rat adrenal gland [Schultzberg et al. (1989) Neuroscience 30, 805-810; Schultzberg et al. (1987) J. Neurosci. Res. 18, 184-189]. In this study, we examine the regulation, upon cholinergic stimulation, of the expression of the cytokine interleukin-1 alpha in the rat adrenal gland. Interleukin-1 alpha and interleukin-1 alpha mRNA levels in the adrenal gland are affected by systemic administration of the cholinergic agonists nicotine (0.5 mg/kg, i.p.) and carbachol (0.5 mg/kg, i.p.). Both drugs cause an increase in interleukin-1 alpha mRNA levels. In contrast to the increased mRNA levels, nicotine and carbachol reduce the interleukin-1 alpha protein level measured in the rat adrenal gland: nicotine by approximately 30%, 60 min after injection, and carbachol by approximately 55%, 30 min after injection. The interleukin-1 alpha protein level returns to control level 90 min after nicotine injection, and 120 min after carbachol injection. We thus found a large, constitutively expressed and inducible pool of interleukin-1 alpha in the rat adrenal gland, which appears to be sensitive to cholinergic stimulation and which may be responsible for some of the local and systemic effects of interleukin-1 alpha. Experiments with Escherichia coli lipopolysaccharide show that this substance, which induces interleukin-1 expression and secretion in macrophages, is also able to induce the expression of interleukin-1 alpha mRNA and interleukin-1 alpha in the adrenal gland when injected at the dose of 2 mg/kg, i.p.
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PMID:Interleukin-1 alpha expression is inducible by cholinergic stimulation in the rat adrenal gland. 164 Nov 33

Superoxide (O2-) and granulocyte elastase (GE) from neutrophils mediate host defense and tissue injury in inflammation. To determine alterations in leukocyte function after trauma, O2- production and GE secretion from neutrophils were studied in trauma patients (n = 20) and healthy controls (n = 15). The priming effect of tumor necrosis factor (TNF), interleukin-1 alpha (IL-1 alpha), and lipopolysaccharide (LPS) on O2- or GE release also was evaluated. Superoxide production (nmole/10 minutes) was elevated significantly in trauma patients at days 0 (9.5 +/- 4.8), 1 (14.2 +/- 7.3), and 3 (12.2 +/- 5.9) and returned to control levels (4.2 +/- 1.6) by day 7. There was no difference in GE secretion between trauma patients and healthy controls. Incubation of neutrophils with TNF induced release of both O2- and GE. Superoxide production was induced by TNF at concentrations at or greater than 10(-11) mol/L. Granulocyte elastase secretion was induced in a time- and dose-dependent manner by TNF at concentrations between 10(-10) and 10(-7) mol/L. In contrast IL-1 alpha and LPS did not potentiate O2- or GE release. These results suggest that neutrophil O2- production increases acutely in trauma. Tumor necrosis factor may mediate this O2- and GE production by neutrophils involved in the inflammatory response.
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PMID:Acceleration of superoxide production from leukocytes in trauma patients. 165 Oct 73

Prostaglandins (PGs) are believed to be involved in some of the manifestations of the acute phase response, which may be triggered by bacterial lipopolysaccharide (LPS). Glucocorticoids are part of this response and, among other things, regulate PG synthesis and are anti-inflammatory. We investigated the role of endogenous and exogenous glucocorticoids in the regulation of aortic prostacyclin synthesis and in its response to LPS. Rats were injected with LPS and their aorta incubated ex vivo. Aortic prostacyclin (PGI2) production declined 1 h after LPS injection and remained low for at least 96 h. On the other hand, LPS stimulated PGI2 production in adrenalectomized rats, although the latter had reduced capacity to synthesize PGI2, compared with sham-operated rats. Dexamethasone substitution restored synthesis. In intact rats only acute (2 h), but not repeated administration of dexamethasone, increased PGI2 production. In vitro IL-1 alpha stimulated aortic PGI2 synthesis. It is concluded that glucocorticoids may exert a biphasic influence on aortic PGI2 production, possibly through a dual action of lipocortins. Moreover, it is suggested that lipocortin requires activation before it can exert its full effect, and that agonists such as LPS may provide the stimulus for such activation.
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PMID:Glucocorticoids regulate prostacyclin synthesis and response to lipopolysaccharide in the rat aorta. 166 48

We investigated the expression of intercellular adhesion molecule-1 (ICAM-1) on primary cultures of human adult oligodendrocytes and astrocytes. Under unstimulated conditions, low levels of ICAM-1 immunoreactivity were identified on both oligodendrocytes (less than 50%) and astrocytes (less than 30%). After 48 hours' exposure to immune mediators, such as culture supernatant of phytohemagglutinin (PHA)-stimulated lymphocytes, interferon gamma (IFN-gamma; 1,000 U/ml), tumor necrosis factor alpha (TNF-alpha; 2,000 U/ml), interleukin-1 alpha (IL-1 alpha; 1,000 U/ml) and lipopolysaccharide (LPS; 50 micrograms/ml), ICAM-1 expression on both cell types was markedly increased in terms of intensity and cell numbers. IFN-gamma and culture supernatant of PHA-stimulated lymphocytes were the most potent inducers of ICAM-1 among the mediators tested, while TNF-alpha, IL-alpha and LPS were less effective, although variations were observed among cultures derived from different donors. Cytokine-induced expression of ICAM-1 on glial cells may play a role in mediating lymphocyte-glial cell interactions at sites of inflammation in the central nervous system.
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PMID:Cytokine-induced expression of intercellular adhesion molecule-1 (ICAM-1) in cultured human oligodendrocytes and astrocytes. 167 9

Brain macrophages (ameboid microglial cells) purified to homogeneity and cultured in vitro synthesize and release IL-1 and TNF upon stimulation with lipopolysaccharide (LPS). This induction can be measured at the levels of transcription and translation. In the present study we have analysed whether certain compounds normally present in the nervous tissue could regulate cytokine production by brain macrophages. We demonstrate that the beta-adrenergic agonist isoproterenol, at a concentration of 10(-7) M; inhibits the LPS-induced transcription and release of TNF alpha. At the same concentration, isoproterenol increases the accumulation of IL-1 alpha and IL-1 beta mRNAs. In spite of its strong effect on IL-1 mRNA accumulation, the adrenergic agonist did not enhance IL-1 activity produced by microglial cells. On the contrary, as is the case for TNF, the LPS-induced production of IL-1 was inhibited by isoproterenol. The effects of isoproterenol on cytokine production specifically involve the beta 2 and not the beta 1 adrenergic receptor. It thus appears (i) that the accumulation of mRNAs coding for TNF alpha on one hand and IL-1 alpha and beta on the other is regulated in two opposite ways by the stimulation of the beta 2-adrenergic receptor and (ii) that mRNA accumulation and cytokine production and secretion are not necessarily coupled.
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PMID:Modulation of interleukin-1 and tumor necrosis factor expression by beta-adrenergic agonists in mouse ameboid microglial cells. 168 49

Solid-phase enzyme immunoassays (with high-turnover acetylcholinesterase as label) for human IL-1 alpha and IL-1 beta were applied to quantify the production of these factors by cultured human umbilical vein endothelial cells (HUVECs). Immunoreactive IL-1s exhibited a typical pattern in HUVECs, under either basal or stimulated conditions: the alpha form was predominant over the beta form and the cell-associated IL-1s measured were more abundant than the material recovered in the supernatants. Bacterial lipopolysaccharide (LPS, 0.5-5 micrograms/ml) significantly increased the basal production of IL-1. Pulses of recombinant IL-1 alpha or -beta or of TNF-alpha followed by a 24 h culture period were also associated with an increased endothelial production of IL-1, with a higher proportion of material secreted in the supernatants as compared with LPS. Other cytokines applied as pulses failed to induce the IL-1s or to modify LPS-induced production of IL-1: they include IL-2, immune interferon, GM-CSF, TGF-beta and EGF. Pharmacological modulators of LPS-induced IL-1 production were identified: glucocorticoids were inhibitors whereas retinoic acid and 1.25-dihydroxy-vitamin D3 had no effects and prostaglandin E2 and IBMX were weak inhibitors. There is no evidence that IL-1 alpha and IL-1 beta are regulated differently in HUVECs, but several significant differences from the monocyte were observed in the regulation of HUVEC IL-1 production.
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PMID:Pharmacological modulation of interleukin 1 production by cultured endothelial cells from human umbilical veins. 169 6

A recently discovered immunosuppressive agent, FK506, has been shown to be effective primarily as an inhibitor of T cell responses in vitro, but little is known about its effects on accessory cell function. This study was undertaken to determine the effect of FK506 on interleukin 1 (IL-1) production by macrophages, by using a sensitive and specific enzyme-linked immunosorbent assay. FK506 partially suppressed IL-1 alpha release, from macrophage-like U937 cells stimulated with phorbol myristate acetate and from human monocytes and alveolar macrophages activated with lipopolysaccharide, in a dose-dependent manner. Moreover, it was indicated that FK506 suppressed not only IL-1 release but also IL-1 synthesis itself, by measurement of cell-associated IL-1 alpha of U937 cells. The optimal concentrations of FK506 for suppressing IL-1 alpha did not affect cell viability or proliferation, and were 10- to 100-fold lower than those of cyclosporin A. It is concluded that FK506 affects macrophage physiology, suppressing IL-1 alpha production significantly. Thus, FK506 has the potency to act on non-T cells and the effect on macrophages may play an additional role in preventing graft rejection.
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PMID:Effects of an immunosuppressant, FK506, on interleukin 1 alpha production by human macrophages and a macrophage-like cell line, U937. 170 47

The purpose of this study was to examine whether Bacteroides (Porphyromonas) gingivalis fimbriae, an important structure involved in attachment of the bacteria to periodontal tissues, activate macrophages and subsequently induce gene expression and production of interleukin-1 (IL-1) in the cells. The fimbriae increased glucose consumption and lysozyme activity in BALB/c macrophages, both criteria of macrophage activation of peritoneal macrophages, in a dose-dependent fashion. A marked increase in the mRNA level of the c-myc gene, an oncogene, in the cells was observed after a 1-h treatment with the fimbriae, and the level decreased rapidly after 3 h. The fimbriae (4 micrograms of protein per ml) markedly induced IL-1 alpha and IL-1 beta gene expression in the cells and IL-1 production. The expression of IL-1 alpha and IL-1 beta genes measured in terms of specific mRNA increased 1 h after the start of treatment and peaked at 6 h. Such increased expression of IL-1 beta was also observed in C3H/HeJ mice, a lipopolysaccharide low-responder strain. The fimbriae stimulated transcriptional activity of IL-1 beta in the cells, but not that of IL-1 alpha. We also observed that fimbriae-induced IL-1 gene expression was not regulated by endogenous prostaglandin triggered by the fimbriae. Therefore, these observations suggest that B. gingivalis fimbriae may be involved in the pathogenesis of adult periodontal disease via triggering of IL-1 production by monocytes/macrophages in periodontal diseases.
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PMID:Bacteroides (Porphyromonas) gingivalis fimbriae activate mouse peritoneal macrophages and induce gene expression and production of interleukin-1. 170 18


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