Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The microtubule (MT) network of the cytoskeleton has been implicated as a mediator of cellular signal transduction; disorganization of this network may allow for mitogenesis. In previous work, loss of MT network organization in human MOLT4 and HUT78 T-cell leukemias was demonstrated in contrast to an organized "spoke-wheel-like arrangement" in normal human T-lymphocytes. In this study, loss of MT network organization was shown in several representative acute myeloid leukemia (AML) cell lines: KG1 myeloblastic, HL60 promyelocytic, and U937 myelomonocytic cells. Re-organization of the MT network was observed in HL60 and U937 AML cells treated with combined lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). This re-organization paralleled earlier work which showed this combination was effective in inducing monocytic pathway differentiation and growth restraint in HL60 cells, and growth restraint in U937 cells. In contrast, KG1 cells exhibited growth restraint, but did not re-organize with LPS/TNF-alpha/IFN-gamma treatment. These results are consistent with a role for the MT network in mitogenesis. Loss of MT network organization appeared to parallel the neoplastic phenotype in three AML cell lines, whereas MT network re-organization accompanied recovery of growth control in 2 of 3 AML cell lines.
 ...
PMID:Growth restraint and differentiation by LPS/TNF-alpha/IFN-gamma reorganization of the microtubule network in human leukemia cell lines. 160 11

The role of macrophage activation in the killing of L. monocytogenes is unclear. Some studies suggest that activation for enhanced production of reactive oxygen and nitrogen intermediates may not be of central importance. Recent data have indicated an important role for interferon-gamma (IFN-gamma) induced retention of L. monocytogenes in endosomes. Data from the present study indicate that proteose peptone-elicited macrophages from DBA2/J, CD-1, and C3H/HeN mice are listericidal. Activation of these cells in vitro for 20 h by IFN-gamma (20 or 500 U/ml) increased H2O2 or nitrite production, but did not increase the number of L. monocytogenes killed during a subsequent 6-h or 7-h culture. Incubation of macrophages with IFN-gamma plus lipopolysaccharide (LPS) caused greater activation and increased the number of Listeria killed during a 6-h or 7-h culture. However, this seems primarily attributable to enhanced phagocytosis. Proteose peptone-elicited macrophages were significantly more effective than resident macrophages in preventing the escape of L. monocytogenes from endosomes into the cytoplasm. This capability was not significantly enhanced by IFN-gamma in vitro, but was enhanced by IFN-gamma plus LPS. This correlates well with the effects of these activation stimuli on killing of L. monocytogenes by proteose peptone-elicited macrophages. These results indicate that enhanced retention of L. monocytogenes in endosomes is induced by proteose peptone elicitation and that further macrophage activation in vitro by IFN-gamma does not improve listericidal activity.
 ...
PMID:Effect of macrophage activation on killing of Listeria monocytogenes. Roles of reactive oxygen or nitrogen intermediates, rate of phagocytosis, and retention of bacteria in endosomes. 160 35

Interleukin 1 (IL-1) production by A/J (A) and C57BL/6J (B6) mouse peritoneal macrophages stimulated with lipopolysaccharide (LPS) was determined. Strain A macrophages produced low levels of soluble IL-1 bioactivity compared with B6 macrophages. This defect was not reversed by indomethacin, interferon-gamma, phorbol myristate acetate, or calcium ionophore A23187. In contrast, cytosolic IL-1 bioactivity was similar in LPS-stimulated A and B6 macrophages. Western blotting revealed that A macrophage supernatants contained lower levels of both 17-kd IL-1 alpha and 17-kd IL-1 beta but similar levels of tumor necrosis factor alpha compared with B6 macrophages. Cytosolic levels of 31-kd pro-IL-1 alpha and also 31-kd pro-IL-1 beta were similar in A and B6 macrophages. Oligonucleotide probing indicated that A and B6 macrophages contained similar levels of IL-1 alpha and also IL-1 beta mRNA. These findings indicate that LPS-stimulated A macrophage culture supernatants contain low levels of both IL-1 alpha and IL-1 beta compared with B6 macrophages and that these defects in IL-1 production are posttranscriptionally regulated.
 ...
PMID:Defective lipopolysaccharide-induced production of both interleukin 1 alpha and interleukin 1 beta by A/J mouse macrophages is posttranscriptionally regulated. 161 93

The GG2EE macrophage tumor cell line was previously established by immortalization of C3H/HeJ mouse bone marrow cells with the J2 retrovirus which contains the v-myc and v-raf oncogenes. Studies on the control of GG2EE cell proliferation in vitro have recently been performed. We observed that the combination of 5-25 U/ml recombinant mouse interferon-gamma (rmIFN-gamma) plus 0.03-0.3 micrograms/ml lipopolysaccharide (LPS) markedly inhibited the proliferation of GG2EE cells (by greater than 95%) in vitro, while either agent alone inhibited only by less than 40% and 0-10%, respectively. Subsequent studies established that biologically active IL1-like (2-4 U/ml) and TNF alpha-like (50-100 U/ml) activities were released into the supernatants of LPS-treated GG2EE cells. The combination of IFN-gamma + LPS induced more (6-8 U/ml) IL1 release. These results suggested that the inhibition of proliferation of GG2EE cells by IFN-gamma + LPS could have been mediated in part by cytokines produced by the cells themselves. rhIL1 alpha at a concentration of 10 U/ml inhibited GG2EE proliferation by 25-30%, while rmIFN-gamma (25 U/ml) + rhIL1 alpha (10 U/ml) inhibited proliferation by 98%. Thus, 10 U/ml rhIL1 alpha could completely replace LPS in the LPS + rmIFN-gamma combination. Further, the combination of low doses of rhIL1 alpha (0.1 to 1 U/ml) plus rmTNF alpha (250 U/ml), which together inhibited proliferation by less than 20% synergized with doses of 5 to 25 U/ml rmIFN-gamma to inhibit proliferation of GG2EE cells by 98-99%. These results suggest that cytokines produced by the cells themselves can synergize with rmIFN-gamma to inhibit the oncogene-driven proliferation of GG2EE cells.
 ...
PMID:Inhibition of proliferation of retrovirus-immortalized macrophages by LPS and IFN-gamma: possible autocrine down-regulation of cell growth by induction of IL1 and TNF. 162 40

Monoclonal antibody H3/5-47 was raised against a human melanoma metastasis and recognizes an antigen expressed in the endothelial cells of all normal human organs as assessed by immunohistochemistry. Antigen expression is higher in venous than in capillary or arterial endothelia; capillary endothelia of different microvascular beds, such as skin, lung, gut or liver, may express varying amounts of this antigen. H3/5-47 antigen expression in the endothelia of diseased tissues (inflammatory diseases, neoplasias) largely reflects its expression pattern in normal tissues. As might be anticipated, the highest expression of H3/5-47 antigen is found in resting adult cutaneous and hepatic cavernous venous hemangiomas. In contrast, psoriatic vessels, characterized by hypertrophy and fenestrations, tend to express H3/5-47 antigen at a much lower density. In human umbilical vein endothelial cells, half the single donor cases show no expression of H3/5-47 antigen, while the rest express the antigen at relatively low densities in about half the cells. Treatment with interferon-gamma or thrombin, but not interleukin-1, lipopolysaccharide, endothelial cell growth factor or phorbolester, either enhances or induces de novo expression in cultured human umbilical vein endothelial cells within 24h; maximum expression of H3/5-47 antigen is induced by interferon-gamma within 72 h. H3/5-47 antigen is not similar to other antigens inducible in human umbilical vein endothelial cells such as HLA-DR, ICAM-1, HECA-452, Leu13, MCP-1 or gamma-IP-10. It is not specifically expressed in the endothelium as it may also recognize certain epithelia, peripheral nervous tissue and bone marrow-derived cell populations.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Monoclonal antibody H3/5-47 recognizes an inducible cell surface antigen expressed differently in endothelium of normal and diseased tissues and in vitro. 162 58

Cytokines such as interleukin-5 (IL-5) and transforming growth factor beta 1 (TGF beta 1) increase IgA production by heterogeneous populations of lipopolysaccharide (LPS)-activated murine B cells. We have used IgA expressing murine B-lymphoma cells CH12.LX.C4.4F10 (4F10) to define the activity of these and other cytokines on IgA secretion at the single-cell level, membrane IgA expression, IgA polymerization and cell growth. IL-5 as well as LPS significantly increases IgA secretion of 4F10 cells, whereas TGF beta 1, a cytokine known to stimulate isotype switching to IgA among surface IgM-bearing B cells, inhibits IgA secretion. When tested alone, IL-1 beta, IL-2, IL-4, IL-6 and interferon-gamma (IFN-gamma) do not significantly alter IgA secretion. However, there is a synergistic increase in IgA secretion when 4F10 cells are co-stimulated with IL-5 and IL-4, while IFN-gamma inhibits IL-5-stimulated up-regulation of IgA secretion. In parallel with increased IgA secretion after cytokine stimulation, 4F10 cells display less membrane IgA. Increased J-chain steady-state mRNA levels after IL-5 or LPS stimulation are paralleled by increased mRNA levels for secreted IgA, but are not accompanied by alterations in the ratio of monomeric to polymeric IgA. IL-5 and LPS initially stimulated but later inhibited 4F10 cell proliferation suggesting an inverse relationship between proliferation and differentiation in this cell line. 4F10 cells are a useful model for the characterization of discrete aspects of IgA B-cell differentiation, since the secretory and membrane Ig and proliferative responses of this IgA B-cell line to cytokines and LPS appear to parallel those of freshly isolated murine B cells.
 ...
PMID:Cytokine-induced differentiation of IgA B cells: studies using an IgA expressing B-cell lymphoma. 163 47

Monocyte-derived macrophages cultured under a variety of conditions were assessed for expression of procoagulant activity (PCA) upon induction by various triggers, using a semiautomated turbidimetric recalcification time assay in a kinetic ELISA reader. Macrophages cultured in a nonadherent (teflon) culture system and seeded in microtiter plates responded with PCA expression to lipopolysaccharide (LPS), to toxic shock-syndrom toxin-1 (TSST-1) and to surface-bound IgG, but not to surface-bound albumin, nor to interferon-gamma (IFN-gamma). In contrast, macrophages stimulated in teflon containers by IFN-gamma showed a strong PCA response peaking around 24 hr after stimulation, but they failed to secrete tumour necrosis factor (TNF). Suspended IFN-gamma-stimulated cells showed a similar response upon 2nd stimulation by LPS or IgG after adherence to microtiter plates as did nonprimed counterparts. In contrast, cells primed in suspension, then cultured in adherence secreted dramatically enhanced amounts of TNF when compared with nonprimed cells. Macrophages stimulated in suspension with LPS showed a PCA response of similar magnitude, which was accompanied by TNF secretion. PCA of both IFN-gamma-primed and LPS-exposed suspension culture cells was largely due to the surface expression of tissue factor, and to a lesser extent of a prothrombinase-like activity, as evidenced by PCA testing with factor-X-deficient plasma. The kinetics of LPS-induced PCA differed from IFN-gamma-induced PCA, in that PCA peaked at 6 hr and fell to insignificant levels after 24 hr. When transferred to microtiter plates at this time, they could be restimulated neither with LPS, nor with surface-adherent IgG nor with IFN-gamma. Evidence was obtained that the failure to express PCA was due to a refractory state of the cells rather than to the generation of cell-bound or secreted inhibitors of coagulation. The loss of PCA expression could be prevented by pre-exposure to IFN-gamma. Thus, PCA expression may be dissociated from other functional and/or activation parameters (e.g. TNF secretion). For the first time, a state in which cells are completely unresponsive to PCA induction has been identified. Should lower LPS concentrations also be found to induce such a refractory state, our results may be of pathophysiological significance.
 ...
PMID:LPS-induced, but not interferon-gamma-induced procoagulant activity of suspended human macrophages is followed by a refractory state of low procoagulant expression. 163 65

We have investigated whether antitumor activity could be expressed independently of cytokine production. Resident macrophages treated with interferon-gamma (IFN-gamma), lipopolysaccharide (LPS) plus muramyldipeptide (MDP) expressed a cytostatic activity against P815 tumor cells and released interleukin 6 (IL-6) and nitrite but produced neither IL-1 nor tumor necrosis factor (TNF). Thioglycollate-elicited macrophages required only LPS plus IFN-gamma for cytostatic activity which was expressed concomitantly with the release of high levels of TNF, IL-1 and IL-6, whereas C3H/HeJ macrophages produced low levels of monokines and were not cytostatic. LPS, alone, was sufficient for triggering Concanavalin A-primed macrophages leading to a full cytostatic activity, even in C3H/HeJ macrophages that was expressed, for these latter, in the absence of monokine production. TNF did not appear to play a role either in autocrine stimulation of macrophages or in the cytostatic process because anti-TNF antiserum affected neither the cytostatic activity nor the nitrite production.
 ...
PMID:Differential stimulation of macrophages for tumor cytostasis and monokine production. 163 11

Ursodeoxycholic acid was recently recognized as an effective agent in the treatment of primary biliary cirrhosis. Experimental evidence supporting the usefulness of ursodeoxycholic acid as a potentially beneficial therapeutic agent for primary biliary cirrhosis has been reported from the biochemical and physiological aspects. In this study, we investigated the direct effects of ursodeoxycholic acid on immunoglobulin and cytokine production in vitro using plaque-forming cell assay and enzyme-linked immunosorbent assay. It was demonstrated that ursodeoxycholic acid suppressed the production of IgM, IgG and IgA induced by Staphylococcus aureus Cowan I in peripheral blood mononuclear cells derived from healthy subjects and patients with primary biliary cirrhosis and also in human B lymphoma cell lines. Furthermore, ursodeoxycholic acid suppressed interleukin-2 and interleukin-4 production induced by concanavalin A and interferon-gamma production induced by polyinosinic-polycytidylic acid, but it did not affect interleukin-1 and interleukin-6 production induced by lipopolysaccharide in peripheral blood mononuclear cells. In addition, ursodeoxycholic acid suppressed the concanavalin A-induced thymocyte proliferation mediated by interleukin-1. Cytotoxicity against lymphocytes was not observed at the concentrations of ursodeoxycholic acid used. These results suggest that the beneficial effect of ursodeoxycholic acid in primary biliary cirrhosis is mediated in part by immunosuppression.
 ...
PMID:Immunomodulatory effects of ursodeoxycholic acid on immune responses. 163 44

We have examined the tissue distribution of 10-kd inflammatory protein (IP-10) mRNA expression in C57Bl/6 mice injected intravenously (i.v.) with various inflammatory stimuli. IP-10 mRNA was strongly induced by interferon-gamma (IFN-gamma) in liver and kidney but only poorly in skin, heart, and lung. IFN-gamma had nearly equivalent access to these tissues as indicated by the distribution of radiolabeled recombinant IFN-gamma 1 h after injection. The time course of IP-10 mRNA appearance was rapid and transient in both liver and kidney; maximal expression in the liver (2 h) preceded that in the kidney (3 h) and declined rapidly thereafter in both tissues. Expression of IP-10 mRNA in the liver and kidney was highly sensitive to IFN-gamma treatment; nearly maximal stimulation occurred with injection of 500 U of IFN-gamma per mouse. Comparable stimulation of IP-10 mRNA expression in splenic macrophages required 10,000 U of IFN-gamma administered i.v., indicating that liver and kidney responses are 10- to 20-fold more sensitive. IP-10 mRNA expression in both tissues was not restricted to stimulation by IFN-gamma but was also seen with injection of lipopolysaccharide (LPS) (25 micrograms/mouse) or IFN-beta (100,000 U/mouse). Two other members of the IP-10 gene family, KC (gro) and JE (MCP-1), were expressed at lower levels under similar treatment conditions. Analysis of IP-10 mRNA distribution in the liver and kidney by in situ hybridization indicated that expression in both tissues was most prominent in the reticuloendothelial cell system, particularly in the endothelial lining of the microvascular circulation. Although the function of the IP-10 gene product has not been defined, these results suggest that it may play an important role in the response of both the liver and kidney to systemic inflammation.
 ...
PMID:Tissue-specific expression of murine IP-10 mRNA following systemic treatment with interferon gamma. 164 Jan 72


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>