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)

In highly purified human polymorphonuclear leukocyte (PMN) preparations containing less than 0.1% contaminating monocytes, significant amounts of interleukin-8 (IL-8) and small amounts of IL-1 alpha, IL-1 beta, and tumor necrosis factor-alpha (TNF-alpha) were produced by lipopolysaccharide (LPS) stimulation. Contrary to published reports, IL-6 production could not be detected. IL-10 inhibited the production of IL-1 alpha, IL-1 beta, IL-8, and TNF-alpha in LPS-stimulated PMNs, as it did in human blood mononuclear cell (MNC) preparations enriched in monocytes. Subsequent investigation of cytokine synthesis inhibitory effect of IL-10 on PMNs was focused on IL-8. IL-10 inhibited IL-8 synthesis in a dose-dependent manner and, in this regard, it was more potent than IL-4 and transforming growth factor-beta 1 (TGF-B1). In both MNCs and PMNs, degradation of LPS-induced IL-8 mRNA was enhanced by IL-10. Furthermore, as determined by nuclear run-on assays, IL-10 inhibited LPS-induced transcription of IL-8 gene in MNCs. However, in PMNs, run-on assays could not reliably detect IL-8 gene transcription. These results provide the first evidence that the human peripheral neutrophil is a target for inhibition of cytokine synthesis by IL-10, and that IL-10 acts by affecting both gene transcription and mRNA stability.
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PMID:Interleukin-10 inhibits interleukin-8 production in human neutrophils. 816 46

We investigated interleukin-10 (IL-10) production in freshly isolated mononuclear cells and purified T cells in response to stimulation with monoclonal antibodies (mAb) recognizing CD3, CD2 and CD28, or with the bacterial products Staphylococcus aureus cells (SAC), staphylococcal enterotoxin (SEA) and lipopolysaccharide (LPS). IL-10 production was compared with that of IL-2, IL-4 and interferon-gamma (IFN-gamma). Similar to the other cytokines, in peripheral blood mononuclear cells (PBMC) from adult donors the highest IL-10 levels were produced in response to CD2 plus CD28 stimulation, within 72-96 hr of stimulation. Levels of IL-10 in response to CD2 plus CD28 stimulation (1.9 +/- 1 ng/ml) exceeded those in response to SEA (0.25 +/- 0.16 ng/ml), SAC (0.43 +/- 0.42 ng/ml), or LPS (0.19 +/- 0.14 ng/ml) stimulation. With adult purified T cells, high levels of IL-10 and IL-4 were measured following CD3 plus CD28 stimulation, and the amounts of both T-helper type-2 (Th2) cytokines decreased following the addition of phorbol myristate acetate (PMA), whereas the synthesis of the Th1 cytokines IL-2 and IFN-gamma was enhanced. When PBMC were stimulated with a CD3 mAb and different other cytokines were added, strong enhancement of IL-10 production was seen upon the addition of IL-2, IL-4, IL-7, IL-12 and IFN-gamma, whereas inhibition was found with transforming growth factor-beta 1 (TGF-beta 1). These data illustrate that in freshly isolated PBMC large amounts of IL-10 can be induced rapidly by appropriate mAb stimulation, and that even in freshly isolated cells IL-4 and IL-10 show signs of parallel regulation.
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PMID:High-level IL-10 production by monoclonal antibody-stimulated human T cells. 855 72

Adhesion of macrophages is a crucial event that determines the number and function of macrophages at inflammatory sites. The aim of this study was to elucidate the role of mesangial cells in the regulation of macrophage adhesiveness. J774.2 macrophages were suspended in serial dilutions of mesangial cell conditioned medium (MC medium) and seeded on plastic tissue culture plates. MC medium did not affect the initial adhesion of macrophages but induced subsequent detachment in a concentration-dependent manner. A similar effect was observed when macrophages were plated on plastic coated with laminin, collagen type IV or Matrigel. The reduced adhesiveness was reversible, and cell viability was unaffected by MC medium, indicating that the effect is not due to cytotoxicity. Conditioned media from fibroblastic, epithelial and endothelial cell lines did not induce macrophage detachment. To identify the active component in MC medium, we examined the involvement of transforming growth factor-beta 1 (TGF-beta 1) in the process. Mesangial cells constitutively expressed TGF-beta 1 mRNA, and MC medium contained the active form of TGF-beta 1. Exogenously added TGF-beta 1 induced macrophage detachment in a dose-dependent manner, and an anti-TGF-beta 1 neutralizing antibody partially abolished the activity of MC medium, indicating the involvement of TGF-beta 1 as an active component. Compared to adherent cells, detached macrophages showed reduced mitogenic activity and blunted induction of IL-1 beta and IL-6 in response to lipopolysaccharide. These data demonstrate that TGF-beta 1 is a mesangial cell-derived factor that impairs adhesiveness of macrophages and confers blunted responses to a specific stimulus. These findings suggest one potential mechanism for macrophage clearance from inflamed glomeruli.
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PMID:Mesangial cell-derived transforming growth factor-beta 1 reduces macrophage adhesiveness with consequent deactivation. 884 Feb 72

Recent evidence indicates that membrane-bound costimulatory molecules of the B7 family are important for T-cell activation and are upregulated in IFN gamma-stimulated human microglia and in multiple sclerosis active lesions. In this study we have performed a detailed analysis of B7-1 and B7-2 expression and regulation in cultured mouse glial cells using immunocytochemical and semi-quantitative reverse transcriptase-polymerase chain reaction techniques. In an immortalized mouse microglial cell line (BV-2), expression of B7-1 and B7-2 was enhanced by interferon-gamma (IFN gamma). IFN gamma was a weak inducer of B7-2 mRNA and immunoreactivity in microglia primary cultures obtained from the neonatal mouse brain, whereas lipopolysaccharide, tumour necrosis factor-alpha, colony-stimulating factors and interleukin-1 beta did not affect microglial B7-2 expression. Combined IFN gamma and lipopolysaccharide treatment very effectively upregulated the B7-2 gene expression and immunoreactivity in microglia, but not in astrocytes. In both glial cell types, expression of B7-1 was not induced by any of the above agents. Among known microglia/macrophage deactivators, interleukin-10, prostaglandin E2 and cAMP-elevating agents, but not transforming growth factor-beta 1 and interleukin-4, inhibited B7-2 transcripts and immunoreactivity in IFN gamma/LPS-stimulated microglia, thus suggesting possible paracrine and autocrine mechanisms for regulating the expression of this important T-cell costimulatory signal in the brain.
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PMID:Analysis of B7-1 and B7-2 costimulatory ligands in cultured mouse microglia: upregulation by interferon-gamma and lipopolysaccharide and downregulation by interleukin-10, prostaglandin E2 and cyclic AMP-elevating agents. 900 48

The release of metals from total joint prostheses may contribute to periprosthetic bone loss manifested as osteolysis. The effects of titanium, cobalt, and chromium on human osteogenic sarcoma cells (osteoblastlike cells) were investigated in vitro. Titanium, cobalt, and chromium at concentrations of 1, 10, and 100 ng/ml did not cause any changes in the cell growth, viability, and injury after 72-hour incubation with the cells. Titanium, cobalt, and chromium at concentrations ranging from 0.01 to 100 ng/ml significantly enhanced the release of interleukin-1 beta and tumor necrosis factor-alpha by lipopolysaccharide stimulated human osteogenic sarcoma cells, whereas they did not alter the release of transforming growth factor-beta 1. Cobalt at concentrations ranging from 0.1 to 100 ng/ml significantly enhanced the release of interleukin-6, but titanium and chromium did not. Cobalt and chromium at concentrations of 10 and 100 ng/ml significantly inhibited the release of osteocalcin by human osteogenic sarcoma cells, whereas titanium had no effect. Titanium, cobalt, and chromium at concentrations of 10 and 100 ng/ml significantly inhibited the synthesis of Type I collagen by human osteogenic sarcoma cells. Cobalt and chromium inhibited the cell proliferation in response to lipopolysaccharide stimulation, whereas titanium did not. The data presented in this article suggest that the metal induced disregulation of cytokine release and osteoblast dysfunction may play an important role in the induction of osteolysis in patients with total joint arthroplasties.
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PMID:Prosthetic metals interfere with the functions of human osteoblast cells in vitro. 918 23

Adenovirus E1A DNA and proteins are frequently detected in lungs of patients with chronic obstructive pulmonary disease. Because adenovirus E1A can regulate host gene expression by interacting with cellular transcription factors, we postulate that E1A enhances synthesis of inflammatory mediators. To examine this possibility, we measured the expression of inflammatory cytokines in E1A-producing A549 human pulmonary epithelial cells and control cells. Interleukin (IL)-8 mRNA was markedly induced by lipopolysaccharide (LPS) in E1A-producing cells but not in controls. IL-8 protein levels were elevated in parallel. In both cell types, monocyte chemotactic and activating factor mRNA induced by LPS was low, and transforming growth factor-beta 1 mRNA was not affected. IL-1 beta, IL-6, granulocyte macrophage colony-stimulating factor, and granulocyte colony-stimulating factor mRNAs were too low to show any effect of E1A. We conclude that the LPS responsiveness of A549 pulmonary epithelial cells is altered by adenoviral E1A by upregulating IL-8. We speculate that this mechanism may be important in the amplification of the inflammatory process of lungs to other irritants.
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PMID:Adenovirus E1A upregulates interleukin-8 expression induced by endotoxin in pulmonary epithelial cells. 922 2

Interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and lipopolysaccharide (LPS) were examined for their ability to regulate the activity and protein levels of inducible nitric oxide synthase (NOS II) in cultured rat colonic smooth muscle cells. Treatment with these agents resulted in a time-dependent increase in NOS II activity. After 48 h, NOS II activity, measured as L-[3H]citrulline production, was increased 24.3 +/- 6.9 pmol.min-1.mg protein-1 by 1 nM IL-1 beta and 3.2 +/- 1.1 pmol.min-1.mg protein-1 by 1 nM TNF-alpha, and increased synergistically by a combination of the two (51.8 +/- 7.3 pmol.min-1.mg protein-1). Measurement of NOS II activity as nitrite production yielded similar results: IL-1 beta, 27.2 +/- 1.2; TNF-alpha, 1.6 +/- 0.1; and IL-1 beta + TNF-alpha, 46.8 +/- 3.2 pmol.min-1.mg protein-1 above basal. LPS (10 micrograms/ml) had a small but significant effect at 48 h that was only additive with that of IL-1 beta. The increase in NOS II activity induced by IL-1 beta and TNF-alpha was inhibited 73-86% by transforming growth factor-beta 1 (TFG-beta 1). The NOS isoform induced by IL-1 beta and TNF-alpha was identified as NOS II by Western immunoblot analysis and confirmed by its 66-97% inhibition by 100 microM S-methylisothiourea, a selective NOS II inhibitor, and its Ca(2+)-independent activity. We conclude that the cytokines IL-1 beta and TNF-alpha act independently and synergistically to stimulate NOS II expression and enzymatic activity in rat colonic smooth muscle through a mechanism sensitive to inhibition by TGF-beta 1.
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PMID:Synergistic regulation of NOS II expression by IL-1 beta and TNF-alpha in cultured rat colonic smooth muscle cells. 945 87

Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a naturally occurring compound shown to inhibit carcinogen-induced preneoplastic lesion formation in mouse mammary organ culture and tumorigenesis in the two-stage mouse skin model. Cancer chemopreventive potential was also suggested in various assays reflective of the three major stages of carcinogenesis. Anti-initiation activity was indicated by its antioxidant and antimutagenic effects, inhibition of the hydroperoxidase function of cyclooxygenase (COX), and induction of phase II drug-metabolizing enzymes. Antipromotion activity was indicated by antiinflammatory effects, inhibition of production of arachidonic acid metabolites catalyzed by either COX-1 or COX-2, and chemical carcinogen-induced neoplastic transformation of mouse embryo fibroblasts. Antiprogression activity was demonstrated by its ability to induce human promyelocytic leukemia (HL-60) cell differentiation. Moreover, pretreatment of mouse skin with resveratrol significantly counteracted 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced oxidative stress, as evidenced by numerous biochemical responses. Resveratrol reduced the generation of hydrogen peroxide, and normalized levels of myeloperoxidase and oxidized-glutathione reductase activities. It also restored glutathione levels and superoxide dismutase activity. As judged by the reverse transcriptase-polymerase chain reaction, resveratrol selectively inhibited TPA-induced expression of c-fos and transforming growth factor-beta 1 (TGF-beta 1), but did not affect other TPA-induced gene products including COX-1, COX-2, c-myc, c-jun, and tumor necrosis factor-alpha. These data indicate that resveratrol may interfere with reactive oxidant pathways and/or modulate the expression of c-fos and TGF-beta 1 to inhibit tumorigenesis in mouse skin. As reported herein, in addition to the activities described above, resveratrol inhibited the de novo formation of inducible nitric oxide synthase (iNOS) in mouse macrophages stimulated with lipopolysaccharide. This finding suggests an additional mechanism by which resveratrol may function as a cancer chemopreventive agent.
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PMID:Cancer chemopreventive activity of resveratrol. 1037 Aug 67

To determine the role of bifidobacteria in the systemic and mucosal antibody response, we examined the direct modulatory effect of bifidobacteria on the synthesis of antibodies by murine spleen B cells. Whole spleen B cells were cultured with Bifidobacterium bifidum or Clostridium perfringens (Welch's bacilli, negative control), and antibody synthesis was measured by ELISA and enzyme-linked immunospot assay. The B. bifidum, but not C. perfringens, substantially increased total secretion of major immunoglobulin (Ig) isotypes and the number of IgA-secreting cells. In addition, B. bifidum increased proliferation of spleen cells by threefold, and C. perfringens had little to diminishing effect on the cells. These results indicate that B. bifidum increased Ig synthesis through its mitogenic influence on B cells. Further, B. bifidum induced spleen B cells to be reactive to transforming growth factor-beta 1 and interleukin-5 and resulted in increased surface IgA expression (approximately threefold) and total IgA production (> 20-fold) but not increased production of IgM and IgG2a isotypes. Together, these studies indicate that B. bifidum can act as a lipopolysaccharide-like polyclonal activator for B cells. Furthermore, that bifidobacteria enable B cells to respond to transforming growth factor-beta 1 and interleukin-5 for the IgA production has important implications for the primary defense against pathogens in the gastrointestinal tract.
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PMID:Bifidobacterium bifidum exhibits a lipopolysaccharide-like mitogenic activity for murine B lymphocytes. 1050 45

The goal of part II of this study was to evaluate the effects of gamma-radiation on circulating blood cells, functional characteristics of splenocytes, and cytokine expression after whole-body irradiation at varying total doses and at low- and high-dose-rates (LDR, HDR). Young adult C57BL/6 mice (n = 75) were irradiated with either 1 cGy/min or 80 cGy/min photons from a 60Co source to cumulative doses of 0.5, 1.5, and 3.0 Gy. The animals were euthanized at 4 days post-exposure for in vitro assays. Significant dose- (but not dose-rate-) dependent decreases were observed in erythrocyte and blood leukocyte counts, hemoglobin, hematocrit, lipopolysaccharide (LPS)-induced 3H-thymidine incorporation, and interleukin-2 (IL-2) secretion by activated spleen cells when compared to sham-irradiated controls (p < 0.05). Basal proliferation of leukocytes in the blood and spleen increased significantly with increasing dose (p < 0.05). Significant dose rate effects were observed only in thrombocyte counts. Plasma levels of transforming growth factor-beta 1 (TGF-beta 1) and splenocyte secretion of tumor necrosis factor-alpha (TNF-alpha) were not affected by either the dose or dose rate of radiation. The data demonstrate that the responses of blood and spleen were largely dependent upon the total dose of radiation employed and that an 80-fold difference in the dose rate was not a significant factor in the great majority of measurements.
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PMID:Dose and dose rate effects of whole-body gamma-irradiation: II. Hematological variables and cytokines. 1149 Oct 15


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