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)

The polypeptide of uromodulin, an immunosuppressive glycoprotein isolated from human urine, has been shown to be identical to that of Tamm-Horsfall glycoprotein and is synthesized exclusively in the kidney (Hession, C., Decker, J. M., Sherblom, A. P., Kumar, S. (1987) Science 237, 1479-1484). Uromodulin binds recombinant murine interleukin 1 alpha with high affinity, and this binding can be inhibited by addition of specific saccharides (Muchmore, A. V., and Decker, J. M. (1987) J. Immunol. 138, 2541-2546). We now report that uromodulin binds recombinant human tumor necrosis factor (rTNF) with high affinity. Both diacetylchitobiose and Man(alpha 1-6)(Man(alpha 1-3]-Man-O-ethyl are effective inhibitors of the binding, whereas a wide variety of other saccharides are not inhibitory. Although Tamm-Horsfall glycoprotein contains predominantly tetraantennary N-linked chains, the binding to rTNF is unaffected by removal of terminal sialic acid, galactose, and N-acetylhexosamine residues. Fractionation of a Pronase digest of uromodulin by gel filtration yields material that inhibits the binding of uromodulin to rTNF but is of lower molecular weight than the major oligosaccharide. Uromodulin does not inhibit the cytotoxic activity of rTNF as monitored by lysis of tumor cell targets but effectively protects mice from lethal challenge with lipopolysaccharide, an event that may involve lymphokine toxicity. We have previously shown that rTNF binds to sections of human kidney and is localized in the same region as uromodulin. Thus, rTNF interacts with uromodulin via carbohydrate chains that are less processed than the major tetraantennary chain, and this interaction may be critical in promoting clearance and/or reducing toxicity of TNF and other lymphokines.
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PMID:The lectin-like interaction between recombinant tumor necrosis factor and uromodulin. 335 92

The purpose of these studies was to establish whether extracellular calcium (Cao2+) plays a role in the process of activation of RAW-264 macrophages for tumor cell killing. We found that these cells were capable of developing a significant level of cytolytic activity under treatment with lymphokine (LK) and lipopolysaccharide (LPS), in the absence of Cao2+ and that responses developed in Ca2+-free media were only 6-18% lower in comparison with the responses developed in the presence of Cao2+. The determination of 45calcium uptake in RAW-264 cells treated with LK and LPS showed that the rate of 45calcium uptake has displayed no increase during either the course of activation or in activated, highly cytolytic cells. Finally, three calcium channel blockers examined here: verapamil, diltiazem and flunarizine, with concentrations ranging from 1 X 10(-7) M - 2.5 X 10(-5) M, showed no inhibitory effect on the process of activation. Nifedipine, another calcium channel blocker, inhibited the development of cytolytic activity with concentrations ranging from 1 X 10(-6) M - 2.5 X 10(-5) M. It could be argued, however, that this inhibition was nonspecific, since this agent was 13 times more potent with regard to the calcium ionophore A23187-induced release of beta-glucuronidase, the function which is entirely dependent on Cao2+. Taken together, these results suggest that Cao2+ is not an absolute requirement for the process of tumoricidal activation of RAW-264 macrophages but it may play some supportive role in this process.
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PMID:Extracellular calcium is not an absolute requirement for tumoricidal activation of RAW-264 macrophage-like cell line. 346 Oct 96

The ability of prostaglandins, glucocorticoids and lipopolysaccharide to modulate I-A expression on macrophages that continuously or transiently express I-A was compared. We found that neither prostaglandins nor glucocorticoids affected I-A expression by macrophages that continuously expressed I-A. In contrast, prostaglandin E2 (PGE2) inhibited the lymphokine-induced maintenance of I-A on macrophages that transiently expressed I-A while glucocorticoids inhibited both the induction and expression of I-A. Lipopolysaccharide caused a loss in the expression of Class II molecules on macrophages that continuously expressed I-A by a prostaglandin-independent mechanism. The lack of effect of PGE2 and glucocorticoids may be related to our observation that continuous expression of I-A does not require its continued synthesis.
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PMID:Modulation of macrophage I-A expression: lack of effect of prostaglandins and glucocorticoids on macrophages that continuously express I-A. 346 86

Secretion of complement component C3 by the mouse macrophage-like cell lines PU5-1.8, J774A.1, RAW264.7, and P388D1 was measured using an enzyme-linked immunosorbent assay for mouse C3. All cell lines secreted antigenically detectable C3 with the relative secreted C3/10(6) cells/24 h ranked as J774A.1 greater than P388D1 greater than or equal to PU5-1.8 much greater than RAW264.7. C3 secretion was enhanced two- to fourfold in cultures of all cell lines when treated with lipopolysaccharide, streptococcal cell walls, or lymphokine-containing supernatant fluids of mitogen-stimulated spleen cells. A differential induction of C3 synthesis and secretion was indicated since secreted lysozyme and total cellular protein were not elevated in a manner comparable to C3. The relative inducibility of cell lines for C3 secretion in either lipopolysaccharide- or cell wall-treated cells could be ranked as PU5-1.8 greater than P388D1 greater than J774A.1 greater than RAW264.7. C3 secretion was inhibited by cycloheximide or hydrocortisone. Mouse macrophage-like cell lines retain baseline and inducible C3 synthetic activities as do normal macrophages and can serve as homogeneous cultures in which to study regulation of complement biosynthesis.
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PMID:Complement component C3 secretion by mouse macrophage-like cell lines. 347 27

The lymphokine B-cell stimulatory factor 1 (BSF-1) has been shown to greatly enhance the differentiation of lipopolysaccharide-activated B cells into IgG1- and IgE-secreting cells in vitro. To determine whether in vivo IgG1 and IgE antibody responses are BSF-1 dependent, the ability of a monoclonal rat IgG1 anti-BSF-1 antibody, 11B11, to affect polyclonal IgG1 and IgE production in mice infected with the nematode parasite Nippostrongylus brasiliensis or injected with a purified goat antibody to mouse IgD was studied. 11B11-containing ascites fluid or purified 11B11 strongly inhibited IgE production in both systems but did not affect IgG1 production, while control ascites or normal rat IgG1 had no IgE-inhibitory activity. These results indicate an important physiologic role for BSF-1 in the generation of IgE antibody responses and suggest means for limiting the production of antibodies responsible for allergic reactions without inhibiting protective antibody responses.
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PMID:Suppression of in vivo polyclonal IgE responses by monoclonal antibody to the lymphokine B-cell stimulatory factor 1. 349 87

In the course of studies of cell-mediated immunity in Graves' disease, we noted that normal peripheral blood monocytes, when stimulated by bacterial lipopolysaccharide, conditioned their media with a factor that had the physicochemical properties of the lymphokine interleukin-1 (IL-1) and that enhanced DNA synthesis and replication in quiescent FRTL5 cells, a line of nontransformed rat thyroid follicular cells. This finding led to the present studies, in which the effect of IL-1 (recombinant IL-1-p) on DNA synthesis in FRTL5 was explored. In the absence of serum, IL-1 induced a small, but significant, increase in [3H]thymidine incorporation into DNA. Calf serum (0.5%) alone also stimulated DNA synthesis slightly, but it greatly enhanced, in a synergistic manner, the stimulatory response to IL-1, decreasing the minimally effective concentration of IL-1 and amplifying the response to higher concentrations. A similar synergism was noted when quiescent FRTL5 were cultured with a combination of IL-1 and a low concentration of insulin-like growth factor-I (IGF-I), which itself stimulated DNA synthesis modestly. IL-1 also increased levels of the mRNA of the proto-oncogene c-myc in quiescent FRTL5, as TSH does, an effect thought to reflect commitment of the cell to increased growth. The findings indicate that IL-1 is an independent stimulator of thyroid cell growth, and that its effects are greatly enhanced by serum, probably in large measure by the IGF-I contained therein. They raise the possibility that IL-1 generated locally by intrathyroid macrophages may act directly by a short-loop mechanism to increase goiter formation in autoimmune thyroid disease.
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PMID:Interleukin-1 stimulates thyroid cell growth and increases the concentration of the c-myc proto-oncogene mRNA in thyroid follicular cells in culture. 349 69

T cell activation is widely believed to depend on interleukin 1 (IL 1) provided by antigen (Ag)-presenting cells (APC). Because IL 1 is not a constitutive product of APC, we examined the features of its production during the interaction of murine T cell clones and APC. We observed that IL 1 was detectable in supernatants of most myoglobin-specific T cell clones grown with APC and Ag. Two of these T cell clones induced exceptionally high levels of IL 1 in their supernatants, and these same clones demonstrated the unusual restriction to I-Ek, which is a low responder type for sperm whale myoglobin. One of these clones was characterized additionally as to the mechanism of IL 1 induction. This clone rapidly stimulated IL 1 production in the APC population (detectable at 4 hr of co-culture) or in macrophages (M phi) or a M phi-like cell line. IL 1 induction was Ag dependent and H-2 restricted. Induction was radioresistant, both on the part of the T cell and of the IL 1 producer. The IL 1-induction process was attributable to a lymphokine produced by the T cell clone. This lymphokine was distinct from IFN-gamma, TNF and CSF-1 and may account for a principal mechanism of T----APC signalling. The induced IL 1 was the same in size, co-mitogenicity, and pyrogenicity as lipopolysaccharide-induced IL 1.
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PMID:IL 1 induction by murine T cell clones: detection of an IL 1-inducing lymphokine. 349 59

Radiolabeled recombinant murine B-cell-stimulatory factor 1 (BSF-1) was used to characterize receptors specific for this lymphokine on the surface of primary B and T cells and in vitro cell lines representing the B-cell, T-cell, mast cell, macrophage, and myelomonocytic lineages. BSF-1 binding was rapid and saturable at 4 degrees C and 37 degrees C with a slow dissociation rate. On all cell types examined, BSF-1 bound to a single class of high-affinity receptor (less than 2000 receptors per cell) with a Ka of 10(10)-10(11) M-1. Receptor expression on resting primary B and T cells was low (less than 100 receptors per cell), whereas activation with lipopolysaccharide or Con A produced a 5- to 10-fold increase in receptor numbers. Among a panel of lymphokines and growth hormones, only unlabeled BSF-1 was able to compete for the binding of 125I-labeled BSF-1. Affinity crosslinking experiments resulted in the identification on all cells tested of a receptor protein with an average Mr of 75,000.
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PMID:Characterization of the high-affinity cell-surface receptor for murine B-cell-stimulating factor 1. 349 45

It has previously been shown that killer-blocking monoclonal antibody (KBA MAb) recognizes lymphokine-activated cell-associated antigen (LAA) involved in broad-reactive killer. (BRK) cell-mediated cytotoxicity. We now report that LAA is expressed on all lymphoid cells, though the amount of LAA on unstimulated lymphocytes is low. In contrast, lymphocytes activated in vitro with either concanavalin A, alloantigens, lipopolysaccharide, or recombinant interleukin 2 express high levels of LAA. In addition, in vivo activated lymphocytes, such as OK-432-activated lymphocytes and tumor-infiltrating lymphocytes express higher levels of LAA than unstimulated lymphocytes. We also demonstrate that the expression of LAA is restricted in T-cell lymphomas and a M phi cell line, while myelomas, fibrosarcomas, and carcinomas do not express LAA. Cell cycle analysis using propidium iodide and KBA MAb showed that LAA expression was closely correlated with the transition of cells from G1a to G1b phase.
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PMID:The role of lymphokine-activated cell-associated antigen. II. Distribution and correlation with cell cycle. 349 48

A series of cloned murine B lymphoma cell lines including WEHI-5, WEHI-231, 2PK-3 and L10A/2J have been studied previously for their ability to present soluble protein antigen in a major histocompatibility complex (MHC) restricted fashion. These B cell lines have been shown to be effective accessory cells in the in vitro stimulation of antigen-specific, MHC-restricted, continuous T cell lines; and in the in vitro stimulation of antigen-specific, MHC-restricted T-T hybridoma cell lines. Using 2PK-3 and L10A/2J as examples of this group of B cell lymphomas we demonstrate in this study that these tumor cell lines constitutively release an interleukin-1 (IL-1) like factor activity as determined by the ability of the conditioned medium from these cultures to support the synergistic stimulation of thymocyte proliferation in the presence of concanavalin A (Con A). Conversely, these same constitutive supernatants will not stimulate the proliferation of IL-2 dependent cell lines such as CTLL-2 or HT-2. Stimulation of 2PK-3 and L10A/2J by lipopolysaccharide (LPS) results in the release of increased levels of the IL-1 like factor activity. By contrast, stimulation of the same cloned 2PK-3 and L10A/2J cell lines with the polyclonal activator Staph. aureus results in the release of a soluble factor activity which functionally acts like IL-2 since conditioned medium from S. aureus stimulated 2PK-3 and L10A/2J cultures will support a CTLL proliferation response as well as stimulate thymocyte proliferation. Thus, the same cloned B cell lines can be differentially stimulated to release lymphokine activity with either IL-1 or IL-2 like functional properties.
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PMID:The same cloned murine B lymphoma cell lines can be selectively induced to release either interleukin-1- or interleukin-2-like factor activity. 349 8


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