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)

This study examined the ability of the recombinant human interleukin 1 receptor antagonist (IL-1ra) to block interleukin 1 (IL-1)-mediated experimental metastases from the A375M human melanoma. In vivo, IL-1ra administrated at concentrations > or = 200 times IL-1 significantly inhibited the increase in lung colonies induced by IL-1 in nude mice. The response to IL-1 was significantly inhibited when IL-1ra was administered simultaneously with or 1 to 3 h before IL-1. In vitro, the incubation of IL-1-activated endothelial cells with IL-1ra prevented the increase in adhesion of A375M melanoma cells. At the same experimental conditions, IL-1ra inhibited the augmented expression of the intracellular and vascular cell adhesion molecules 1 and E-selectin induced by IL-1 on endothelial cells. Lipopolysaccharide, an IL-1 inducer, increased the number of lung colonies in nude mice. IL-1ra injected with or 1 h after lipopolysaccharide inhibited this augmentation, suggesting a role for host-produced IL-1 in metastasis formation.
 ...
PMID:Interleukin 1 receptor antagonist inhibits the augmentation of metastasis induced by interleukin 1 or lipopolysaccharide in a human melanoma/nude mouse system. 826 95

Our purpose was to evaluate the ability of blood monocytes of renal cancer patients to become cytotoxic against fresh, autologous tumor cells. Fresh target cells were obtained by mechanical enzymatic dissociation of tumor and normal renal tissue. The A375 cell line, derived from a human melanoma, and the SW626 cell line, derived from a human ovarian carcinoma, were used as positive target cell controls. Monocytes from renal cancer patients and normal volunteers were activated in vitro with lipopolysaccharide (LPS), or muramyl tripeptide (MTP-PE), or multilamellar vesicle liposomes containing MTP-PE (MLV-MTP-PE), with or without a pre-incubation with r-IFN-gamma, and tested for cytotoxicity in a 72-hr 111Indium-release assay. All patients were tumor-free at the time of the monocyte study. No difference in cytotoxic activity was observed between monocytes from healthy volunteers and those from cancer patients. Freshly dissociated tumor cells were as susceptible to tumoricidal monocytes as the 2 cell lines. Moreover, no cell population appeared to be resistant to activated monocytes, which were cytotoxic to both allogeneic and autologous fresh tumor cells. Activated monocytes maintained their ability to discriminate between normal and neoplastic cells and were not cytotoxic against autologous or allogeneic normal non-neoplastic cells. Our data indicate that MLV MTP-PE liposomes activate peripheral blood monocytes from cancer patients to a tumoricidal status against fresh, dissociated non-cultured autologous tumor cells.
 ...
PMID:Activation of cytolytic activity in peripheral blood monocytes of renal cancer patients against non-cultured autologous tumor cells. 837 21

The purpose of these studies was to determine whether triggering murine peritoneal macrophages to a tumoricidal state by lipopolysaccharide (LPS) requires protein-tyrosine phosphorylation. The LPS-triggered activation of mouse macrophages to lyse syngeneic B16 melanoma cells was significantly inhibited in a dose-dependent manner by the protein-tyrosine kinase (PTK) inhibitors genistein, herbimycin A, and tyrphostin. Genistein was effective only when added to macrophages prior to or simultaneously with LPS. Genistein potently inhibited the productive interaction of macrophages with LPS but had only a minor effect on the action of interferon-gamma. The effects of genistein on LPS-triggered macrophage activation were not due to nonspecific changes in macrophage metabolism or toxicity because genistein did not prevent lysis of tumor cells by activated macrophages, nor did it reduce the capacity of macrophages to phagocytose antibody-opsonized sheep erythrocytes. Western blot analysis with antiphosphotyrosine monoclonal antibody revealed that incubation of macrophages with LPS produced a rapid increase in tyrosine phosphorylation of several proteins and that the induced phosphorylation could be inhibited by effective concentrations of genistein, herbimycin A, or tyrphostin. Taken together, these data indicate that protein-tyrosine phosphorylation plays an important role in LPS-induced tumoricidal activation of macrophages.
 ...
PMID:Activation of tumoricidal properties in macrophages by lipopolysaccharide requires protein-tyrosine kinase activity. 842 92

Potent chemotactic activity for neutrophils was detected in rat inflammatory exudate induced by a subcutaneous injection of lipopolysaccharide in a carboxymethyl-cellulose suspension. We purified and characterized chemoattractants from the exudate by the following procedures: carboxymethyl-Sephadex C-25 ion-exchange chromatography; G3000SW gel-filtration chromatography; preparative reverse-phase high-pressure liquid chromatography; rechromatography on reverse-phase HPLC. Two chemotactic factors were purified and their N-terminal amino acid sequences were determined. One factor was a protein in which the first 20 N-terminal amino acids were identical to those of rat cytokine-induced neutrophil chemoattractant (CINC), a counterpart of human gro/melanoma growth-stimulating activity (MGSA). The other factor was highly similar to mouse macrophage inflammatory protein 2 (MIP-2). Mouse MIP-2, a chemotactic factor for neutrophils, is a member of the interleukin-8 family; however the protein we purified had higher similarity to human gro/MGSA than to human interleukin-8. These results indicate that, in rats, chemotactic factors for neutrophils induced by lipopolysaccharide stimulation are not counterparts of interleukin-8, but are gro/CINC-related peptides.
 ...
PMID:Chemoattractants for neutrophils in lipopolysaccharide-induced inflammatory exudate from rats are not interleukin-8 counterparts but gro-gene-product/melanoma-growth-stimulating-activity-related factors. 850 97

The purpose of this study was to investigate the ability of the antimalarial drug, Ro 42-1611 to block parasite mediated cytokine induction in vitro as well as cytoadherence of infected erythrocytes to melanoma cells in vitro. The biological activity of Ro 42-1611 was confirmed as it blocked Plasmodium falciparum growth in cultures. Ro 42-1611, had no major effect on TNF, IL-alpha or IL-6 cytokine release from mononuclear cells stimulated with malaria antigens or lipopolysaccharide and it did not affect cell viability. Ro 42-1611 only slightly suppressed cytoadherence of infected erythrocytes to melanoma cells. The therapeutic effect of To 42-1611 appears to be confined to its parasite killing activity.
 ...
PMID:The antimalarial drug, Ro 42-1611 (arteflene), does not affect cytoadherence and cytokine-inducing properties of Plasmodium falciparum malaria parasites. 852 91

The glucocorticoid dexamethasone inhibited the production of the rat cytokine-induced neutrophil chemoattractant CINC/gro, a counterpart of human melanoma growth-stimulating activity that belongs to the interleukin-8 (IL-8) family, in the normal rat kidney epithelial cell line NRK-52E stimulated with interleukin-1 beta (IL-1 beta), lipopolysaccharide, or tumor necrosis factor alpha. The accumulation of CINC/gro mRNA induced by these activators was also decreased comparably by dexamethasone. A nuclear run-on assay revealed that dexamethasone decreased the IL-1 beta-induced transcription of the CINC/gro gene. The half-life of CINC/gro mRNA transcripts did not change significantly after exposure to dexamethasone, suggesting that this glucocorticoid acts mainly at the transcriptional level. Transfection with luciferase expression vectors containing 5'-deleted and mutated CINC/gro gene sequences demonstrated that the 5'-flanking region containing the NF-kappa B binding site is involved in the IL-1 beta- and dexamethasone-induced activation and repression of the CINC/gro gene expression, respectively. Furthermore, a tandem repeat of the NF-kappa B sequence in the CINC/gro gene conferred the inducibility by IL-1 beta and suppression of luciferase activity by dexamethasone. In an electrophoretic mobility shift assay, dexamethasone diminished the IL-1 beta-induced formation of NF-kappa B complexes, which consisted of p65 and p50. Western blotting revealed that dexamethasone inhibited the IL-1 beta-induced translocation of p65 from the cytoplasm into the nucleus, while the nuclear level of NF-kappa B p50 remained almost unchanged. In addition, the degradation of I kappa B-alpha induced by IL-1 beta was not inhibited by dexamethasone. These results indicated that the suppression of the CINC/gro gene transcription by glucocorticoid occurs through the impairment of NF-kappa B activation, possibly by interference with the translocation of NF-kappa B p65 from the cytoplasm into the nucleus, thereby suppressing transactivation of the CINC/gro gene.
 ...
PMID:Glucocorticoid-mediated gene suppression of rat cytokine-induced neutrophil chemoattractant CINC/gro, a member of the interleukin-8 family, through impairment of NF-kappa B activation. 857 66

In order to expand tumor-infiltrating lymphocytes (TIL) efficiently and in order to use them for immunotherapy, we utilized lipopolysaccharide-activated B cells (LPS blasts) as costimulatory-signal-providing cells in an in vitro culture system. TIL, prepared from subcutaneously inoculated B16 melanoma, failed to expand when cultured with anti-CD3 monoclonal antibody (mAb) alone followed by a low dose of interleukin(IL)-2. In contrast, such TIL did expand efficiently in culture with both anti-CD3 mAb and LPS blasts followed by culture with IL-2. These findings suggest that the presence of LPS blasts in the initial culture was essential for the cell expansion. The expansion of TIL was partially blocked by the addition of CTLA4 Ig, which is an inhibitor of costimulatory molecules such as CD80 and CD86, and was almost blocked by the addition of anti-(Fc receptor gamma II)mAb. These findings thus indicate that such molecules, in conjunction with the receptor on the LPS blasts, participate in the efficient expansion of TIL. The B16-derived TIL, which expanded in our culture system, were predominantly CD8+ T cells and showed a higher level of cytolytic activity against B16 melanoma than either lymphokine-activated killer cells or TIL cultured with a high dose of IL-2. In addition, the in vitro expanded B16-derived TIL produced interferon gamma, but not IL-4, in response to B16 melanoma. What is more important, the adoptive transfer of such TIL had a significant antitumor effect against pulmonary metastasis in B16 melanoma, even without the concurrent administration of IL-2. Collectively, our results thus indicate the therapeutic efficacy of the protocol presented here for antitumor immunotherapy with TIL.
 ...
PMID:Specific antitumor activity of tumor-infiltrating lymphocytes expanded first in a culture with both anti-CD3 monoclonal antibody and activated B cells and then in a culture with interleukin-2. 863 91

Cytotoxicity indicated by increased release of prelabeled 51chromium (51Cr) and lactate dehydrogenase (LDH) was studied in human prostate cancer and melanoma cells in cell culture following irradiation or exposure to several injurious substances. These changes were compared to those observed in bovine aortic endothelial cells (BAEC) subjected to identical treatments. Further, the effect of irradiation on plasminogen activator (PA) secretion from prostate cancer cells, and the effect of glycine on radiation-induced cytotoxicity in BAEC were also investigated. Radiation, lipopolysaccharide and xanthine/xanthine oxidase stimulated no release of 51Cr or LDH from tumor cells, while these treatments induced a dose- and time-related loss of those cytotoxic indicators from BAEC. Protease, elastase and Triton X-100 incited loss of 51Cr and LDH from all three cell types. Radiation, lipopolysaccharide and xanthine/xanthine oxidase have been shown to cause cell injury via a common pathogenic pathway of oxidant generation. Tumor cells appear quite resistant to oxidant stress. Cell damage precipitated by protease, elastase and Triton probably involves hydrolysis of proteins and phospholipids in the cell membrane, leading to an increased leakage of intracellular proteins such as LDH and those bound with 51Cr. Radiation caused a dose- and time-related reduction in the secretion of PA from prostate cancer cells. PA is alleged to play a role in tumor metastasis; the reduced secretion could be another beneficial effect of radiation, in addition to interruption of cell proliferation, in the impediment of tumor growth and spread. Glycine diminished cytotoxic injury of BAEC inflicted by radiation. This amino acid may prove useful in offering a degree of protection of normal tissue against radiation associated side-effects.
 ...
PMID:Injury-specific cytotoxic response of tumor cells and endothelial cells. 868 34

Nitric oxide (NO) may be an important mediator of tumour angiogenesis and metastasis formation. Tumour cell derived NO may be important in the regulation of angiogenesis and vasodilatation of the blood vessels surrounding a tumour. The aims of the present study were, firstly, to determine whether malignant melanoma cells and normal melanocytes had nitric oxide synthase (NOS) activity (measured by the conversion of L-arginine to L-citrulline) and, secondly, to determine whether there was a difference in NOS activity between malignant and normal cell types. This paper assays NOS activity directly in lysates from normal human melanocyte and malignant melanoma cell lines. The enzyme activity was not inducible with bacterial lipopolysaccharide and could be heat denatured. The activity of NOS was demonstrated to be both NADPH- and calcium-dependent and it was inhibitable in a dose-dependent manner by the NOS inhibitor Nw-nitro-L-arginine methyl ester. We conclude that melanoma and melanocyte cells express a constitutive form of NOS. Finally, nitric oxide synthase activity in melanoma cell lines was found to be significantly greater than in normal melanocytes. These findings suggest that NO synthesis is elevated in malignant melanoma. An elevated NO concentration in melanoma is expected to promote metastases by maintaining a vasodilator tone in the blood vessels in and around the melanoma.
Melanoma Res 1996 Apr
PMID:Nitric oxide synthase activity is up-regulated in melanoma cell lines: a potential mechanism for metastases formation. 879 Dec 69

The intercellular adhesion molecule (ICAM) 1 is an Ig-like cell adhesion molecule expressed by several cell types, including leukocytes and endothelial cells. It can be induced in a cell-specific manner by several cytokines, for example, tumor necrosis factor-alpha, interleukin-1, and interferon-gamma, and inhibited by glucocorticoids. Its ligands are the membrane-bound integrin receptors LFA-1 and Mac-1 on leukocytes, CD43, the soluble molecule fibrinogen, the matrix factor hyaluronan, rhinoviruses, and Plasmodium falciparum malaria-infected erythrocytes. ICAM-1 expression is predominantly transcriptionally regulated. The ICAM-1 promoter contains several enhancer elements, among them a novel kappa B element which mediates effects of 12-O-tetradecanoylphorbol-13-acetate, interleukin-1, lipopolysaccharide, tumor necrosis factor-alpha, and glucocorticoids. Expression regulation is cell specific and depends on the availability of cytokine/hormone receptors, signal transduction pathways, transcription factors, and posttranscriptional modification. ICAM-1 plays a role in inflammatory processes and in the T-cell mediated host defense system. It functions as a costimulatory molecule on antigen-presenting cells to activate MHC class II restricted T-cells, and on other cell types in association with MHC class I to activate cytotoxic T-cells. ICAM-1 on endothelium plays an important role in migration of (activated) leukocytes to sites of inflammation. ICAM-1 is shed by the cell and detected in plasma as sICAM-1. Regulation and significance of sICAM-1 are as yet unclear, but sICAM-1 is increased in many pathological conditions. ICAM-1 may play a pathogenetic role in rhinovirus infections. Derangement of ICAM-1 expression probably contributes to the clinical manifestations of a variety of diseases, predominantly by interfering with normal immune function. Among these are malignancies (e.g., melanoma and lymphomas), many inflammatory disorders (e.g., asthma and autoimmune disorders), atherosclerosis, ischemia, certain neurological disorders, and allogeneic organ transplantation. Interference with ICAM-1 leukocyte interaction using mAbs, soluble ICAM-1, antisense ICAM-1 RNA, and in the case of melanoma mAb-coupled immunotoxin, may offer therapeutic possibilities in the future. Integration of knowledge concerning membrane-bound and soluble ICAM-1 into a single functional system is likely to contribute to elucidating the immunoregulatory function of ICAM-1 and its pathophysiological significance in various disease entities.
 ...
PMID:Intercellular adhesion molecule-1. 883 67


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