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)

We obtained peripheral blood mononuclear cells (PBMC) from four healthy, tuberculin purified protein derivative (PPD) reactive donors and cultured these cells in media containing PPD (low dose = 200 ng/ml or high dose = 1 micrograms/ml). Five days after the addition of PPD, T cells were isolated, washed, and added to autologous adherent cell cultures at a 1:1 ratio. Adherent cells were then cultured for 24 h in media only (baseline), media plus lipopolysaccharide (LPS, 2 micrograms/ml; positive control), or media containing the prestimulated T cells. After 24 h, supernatants were harvested and interleukin 1 beta (IL-beta) levels were assayed by radioimmunoassay (RIA) or enzyme-linked immunosorbent assay (ELISA). The results show that T cells prestimulated with low dose PPD (200 micrograms/ml) did not induce IL-1 production by adherent cells (mean increase over baseline 0.2 +/- 1.3 standard deviation [SD] ng/ml, P = 0.61). However, T cells prestimulated with high dose PPD (1 microgram/ml) did induce adherent cells to secrete IL-1 beta (mean increase over baseline 1.7 +/- 0.62 [SD] ng/ml, P = 0.01), but this induction was abolished when cell-to-cell contact was prevented by use of double well chambers (mean increase over baseline 0.1 +/- 0.36 [SD] ng/ml, P = 0.69). Prestimulated T helper (CD4+) cells were able to induce monocytes to secrete IL-1 beta but prestimulated CD8+ T cells were not. These data suggest that when T helper (CD4+) cells are sufficiently activated they acquire the ability to induce monocytes to secrete IL-1 beta. Cell-to-cell contact between monocytes and T cells is required. This function of activated T cells may be important in the normal cellular immune response.
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PMID:T helper/inducer (CD4+) cells prestimulated with PPD induce monocytes to produce interleukin-1 beta. 167 91

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

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

Substance P (SP) is an undecapeptide with neurotransmitter and immunoregulatory properties. In murine schistosomiasis, ova naturally induce liver and intestinal granulomas. These granulomas contain macrophages, and eosinophils that produce SP. A report showed that human blood monocytes isolated by adherence release interleukin-1 (IL-1) in response to SP (Lotz et al. (1989) Science 241, 1218). IL-1 is important for initiation of hypersensitivity granulomas. Therefore, it was determined whether SP modulates granuloma macrophage IL-1 production in murine schistosomiasis. Macrophages were obtained from lung and liver granulomas, and from spleens of infected mice. A thymocyte proliferation assay measured IL-1 activity in culture supernatants. Total RNA, extracted from macrophages, was assayed for IL-1 alpha and beta mRNA by Northern blotting using cDNA probes. In response to lipopolysaccharide (LPS), splenic macrophages and macrophages from young lung granulomas released appreciable IL-1. Macrophages from liver granulomas, that were lesions older than the lung granulomas, were unresponsive to LPS with regard to IL-1 secretion. Yet, granuloma macrophages spontaneously expressed IL-1 alpha and beta mRNA. LPS enhanced IL-1 mRNA expression in both splenic and granuloma macrophages. Exposure of macrophages from all sources to SP did not alter IL-1 secretion or gene expression. Similarly, the responsiveness of macrophages to LPS was not affected by concomitant exposure to SP. It is concluded that, in the murine system, SP does not directly influence splenic or granuloma macrophage IL-1 secretion or gene expression. Also, it appears that macrophage secretion of IL-1 is rapidly down-regulated following granuloma elicitation.
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PMID:Substance P does not alter interleukin-1 expression by splenic or granuloma macrophages in murine schistosomiasis. 171 19

Tissue factor (TF) is the first factor of the extrinsic pathway of coagulation. Normally, TF is not expressed on the surface of endothelial cells. However, expression of TF can be induced in these cells in response to stimulation by diverse inflammatory mediators such as interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), lipopolysaccharide (LPS), and phorbol 12-myristate 13-acetate (PMA). We have studied the effect of these mediators on the kinetics of the induction of TF-related procoagulant activity (PCA) on human umbilical vein endothelial cells (HUVECs). PCA is transiently induced on HUVECs, attaining a peak some 4 to 8 hours after addition of inflammatory agents, with maximal accumulation of TF messenger RNA (mRNA) occurring 3 to 5 hours earlier. Because the expression of PCA by treated HUVECs returns to basal levels by 20 to 30 hours, we examined the response of these cells to a second inflammatory stimulus. Continuous incubation of cells with a single inflammatory agent for 24 to 48 hours induces a hyporesponsive state with respect to the reinduction of TF expression by the same agent (14% of the initial stimulation for IL-1 beta, 39% for TNF-alpha 30% for LPS, and 7% for PMA). Such a diminution in PCA was also observed in the levels of TF mRNA. By contrast, pretreatment of HUVECs with one agent did not dramatically affect the reinduction of TF by any of the three other factors. We subsequently focused our attention on the induction of the autologous refractory period by IL-1 beta. De novo protein synthesis was not required during the preincubation of ECs for hyporesponsiveness to be observed. The establishment of the refractory state did not depend on the downmodulation of IL-1 beta receptor affinity or expression. Moreover, pretreatment of HUVECs with IL-1 beta increased prostacyclin (PGI2) production in response to a second stimulation by IL-1 beta, although such cells were unable to reexpress TF under the same conditions. This result suggests that distinct secondary messenger pathways are involved in TF induction and PGI2 synthesis by IL-1 beta in HUVECs.
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PMID:Refractory period phenomenon in the induction of tissue factor expression on endothelial cells. 171 79

In this in vitro study, the influence of serum-concentration, heat inactivation of the serum and the origin of the serum on the responsiveness of cultured human umbilical vein endothelial cells (HUVEC) to immunological challenges was investigated. Addition of human serum during stimulation with 1 microgram/ml bacterial lipopolysaccharide (LPS) increased endothelial cell ELAM-1 expression and interleukin (IL)-6 release five to ten-fold. Full endothelial cell responsiveness to LPS required 10 to 50% human serum and was largely abrogated after heating the serum for 30 minutes at 56 degrees C. Addition of newborn or fetal bovine serum instead of human serum, induced even higher IL-6 release and ELAM-1 expression in response to LPS, whilst heat-inactivation of these serum-batches only moderately decreased endothelial cell responses. Endothelial cell IL-6 release and ELAM-1 expression after stimulation with IL-1 beta and tumor necrosis factor-alpha (TNF-alpha) were less influenced by heat inactivation of the serum and by omission of serum, whilst responses to PMA remained completely unaffected by such modifications in assay media. Finally, we demonstrated that endothelial cell IL-8 release also and ICAM-1 expression in response to LPS and cytokines were increased by addition of human serum, indicating that the use of serum-free assay media, or the use of media enriched with heat-inactivated (HI) human serum interferes with physiological endothelial cell responsiveness.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:LPS and cytokine-induced endothelial cell IL-6 release and ELAM-1 expression; involvement of serum. 172 50

The capacity of human monocytes/macrophages (M/M) infected with a human immunodeficiency virus-1 (HIV-1) isolate to produce several immunomodulating cytokines including interleukin-1 alpha (IL-1 alpha), IL-1 beta, tumor necrosis factor-alpha (TNF-alpha), IL-6, IL-8, and macrophage chemoattractant and activating factor (MCAF) was examined. Although HIV infection itself induced significant increases in the level of mRNAs for IL-1 beta, TNF-alpha, IL-6, and IL-8, the levels of lipopolysaccharide (LPS)-induced mRNAs for IL-1 alpha, IL-1 beta, TNF-alpha, IL-6, IL-8, and MCAF were decreased over those of uninfected LPS-stimulated cells. In addition, HIV-infected M/M produced lower amounts of IL-8 protein, as measured by radioimmunoassay over an 18-day culture period. These results suggest that HIV infection generally suppresses the LPS-inducible cytokine production in human M/M. The impact of the role of these cytokines in the immunity and pathogenesis of HIV-1 infection is discussed.
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PMID:Decrease in cytokine production by HIV-infected macrophages in response to LPS-mediated activation. 172 30

We recently reported an abnormal production of interleukin-1 (IL-1) in peripheral macrophages of several neurological mutant mice that exhibit patterns of neuronal degeneration, especially in the cerebellum. After in vitro activation by lipopolysaccharide acid (LPS), these macrophages hyperexpress IL-1 beta mRNA and hyperproduce IL-1 protein in comparison with +/+ controls. In the present study, focused on the staggerer mutant mice, we investigate if this genetic dysregulation is specific for IL-1 beta or if it reflects a generalized hyperexcitability of these macrophages. The hyperexpression of IL-1 beta mRNA in sg/sg macrophages is present whatever the duration of LPS stimulation, even for periods as short as 15 min, although it reaches a maximum after 4 h of stimulation. The hyperinducibility of sg/sg macrophages is observed even when very low doses of LPS are used (0.01 microgram/ml) and reaches its maximum for 5 micrograms/ml LPS. Synthetic molecules (muramyl dipeptides), such as N-acetylmuramyl-L-alanyl-D-isoglutamine or murabutide, known as macrophage activators, are also efficient in revealing the cytokine hyperexpression in sg/sg macrophages. In addition, hyperexpression of two other cytokines, i.e., tumor necrosis factor-alpha and IL-1 alpha mRNAs, is also detected in LPS-stimulated macrophages of mutant mice. Finally, the effect of an inhibitor of protein synthesis, cycloheximide, is similar in +/+ and sg/sg macrophages. As a whole, these data lead us to conclude that the sg/sg macrophages are in a state of general hyperexcitability when compared with +/+ ones.
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PMID:Evidence for a hyperexcitability state of staggerer mutant mice macrophages. 172 30

Chemotactic cytokines play a critical role in recruiting leukocytes to sites of tissue injury. Interleukin-8 (IL-8) is a chemotactic cytokine secreted by a variety of cells (eg, monocytes, endothelial cells, fibroblasts) during the inflammatory response. In this report, the authors demonstrate that human transitional cell carcinomas and renal cell carcinomas have the capacity to elaborate IL-8 in response to the inflammatory mediators IL-1 beta and tumor necrosis factor (TNF)-alpha. All cell lines expressed high levels of IL-8 mRNA on stimulation with either IL-1 beta or TNF-alpha, but not lipopolysaccharide; one expressed the gene constitutively. The authors selected one transitional cell carcinoma cell line (UM-UC-9) and one renal cell carcinoma cell line (UM-RC-5) for further study. Both displayed a time- and dose-dependent increase in steady-state levels of IL-8 mRNA in response to IL-1 beta and TNF-alpha. Specific mRNA was detectable by 1 hour after stimulation. Secretion of antigenic IL-8 measured by enzyme-linked immunosorbent assay into culture supernatants reflected the kinetics of mRNA expression. Because heat-inactivated TNF-alpha failed to induce synthesis of IL-8 mRNA, and cycloheximide augmented TNF-alpha-induced synthesis, IL-8 expression appears to be a stimulus-specific primary induction phenomenon. As with other inflammatory mediators whose mRNA contains a 3' AU-rich sequence (eg, IL-2, TNF-alpha), the half-life of IL-8 mRNA was short, less than 1 hour. Our data suggest that secretion of IL-8 by malignant cells may partly account for the inflammatory infiltrates associated with some malignant neoplasms.
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PMID:Cytokine-induced gene expression of interleukin-8 in human transitional cell carcinomas and renal cell carcinomas. 173 30


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