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)

A protein purified from Eschericheri coli has previously been shown to have cytotoxic effects on neoplastic cells of several lineages both in vitro and in vivo. Accordingly, this protein has been named anti-neoplastic protein (ACP). Although ACP kills neoplastic cells by inducing apoptosis, it has negligible effects on various normal cells. In addition to the direct cytotoxic effects of ACP on tumour cells, previous studies have shown that in vivo ACP increases tumouricidal activity of cytotoxic lymphocytes. We investigated whether cytokines from host or tumour cells play a part in the enhanced cellular immunity seen in ACP-treated tumour-bearing mice. Growth of normal human keratinocytres (KC) was not significantly affected by subnanogram amounts of ACP, however ACP dose-dependently killed KHT cells, a murine fibrosarcoma cell line (LD50 = 8 x 10(4) ng/cell). as well as the human squamous carcinoma cell line COLO-16 (LD50 = 2.5 x 10(-4) ng/cell). Testing purified ACP on cultures of normal keratinocytes and squamous carcinoma cell lines revealed that ACP could induce both mRNA and protein for interleukin-6 (IL-6). Messenger RNA for IL-6 increased dose-dependently 4h after treatment of COLO-16 squamous carcinoma cells with 10(-4) to 10(-2) ng/cell ACP. Maximal increment was 50-fold. Interleukin-6 message remained elevated up to 24h later in both normal keratinocytes and squamous carcinoma cultures treated with ACP. Conditioned supernates from these cultures were analysed by ELISA and found to have 4-fold higher levels of IL-6 protein than untreated cells after 4h. After 24h, IL-6 did not increase above the 4h level. Boiling of the ACP preparation showed that the cytokine induction was not due to contaminating lipopolysaccharide. The cytoxic effect of ACP on tumour cells in vitro was not due to IL-6 protein induction since neither recombinant IL-6, nor the other proinflammatory cytokines, IL-1 alpha or Tumour necrosis factor-alpha (TNF-alpha) (0.1-10ng/ml) were able to kill malignant cells. We demonstrated IL-6 gene induction by ACP in the squamous carcinoma lines as well as in normal KC. This suggests that the in vivo effectiveness of ACP against tumours may be due to stimulatory effects of IL-6 on host immunity.
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PMID:Augmentation of interleukin-6 (IL-6) expression in squamous carcinoma cells and normal human keratinocytes treated with recombinant anti-neoplastic protein (ACP). 807 68

A lipopolysaccharide (BP-LPS) isolated from killed Bordetella pertussis (Tohama strain) was determined to have low toxicity based on the mortality and decrease in body weight of BP-LPS-injected mice. BP-LPS, administered intradermally or intraperitoneally, clearly inhibited the growth of an MM46 murine mammary carcinoma. When compared with a toxic Escherichia coli-derived LPS, BP-LPS displayed excellent anti-tumour activity against MH134 hepatoma and Meth A fibrosarcoma. As part of a combined chemotherapy/immunotherapy regimen, BP-LPS also seemed to prolong the lifespan of mice inoculated with Lewis lung carcinoma. BP-LPS thus appears to have valuable characteristics as an anti-tumour agent.
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PMID:Anti-tumour activity of low-toxicity lipopolysaccharide of Bordetella pertussis. 819 67

The effect of morphine on tumor growth of EL-4 leukemia in C57BL/6 mice and of Sarcoma 180 carcinoma in ddY mice was studied. Local subcutaneous tumor growth was enhanced by morphine (10 mg/kg, s.c.) given daily for 10d. This effect was inhibited by preadministration of the opioid antagonist naloxone. However, naloxone alone had no significant effect on tumor growth. Morphine also enhanced tumor growth in C57BL/6 mice inoculated i.p. with P388 as well as Meth-A cell in Balb/c mice. However, incubation of morphine with cultures of EL-4, P388, MM-46 and Meth-A cells failed to enhance tumor growth. Mice given morphine displayed marked atrophy and reduced cellularity of the spleen and thymus. The humoral response to sheep erythrocytes and T- and B-cell responses to foreign antigens were suppressed, and the lymphocyte proliferative response to T- and B-cell mitogens (concanavalin A and bacterial lipopolysaccharide, respectively) was attenuated. Morphine exerted an inhibitory effect on the immune response which was antagonized by the concomitant administration of naloxone. These data suggest that the enhancement of tumor growth by the administration of morphine is the result of a overall immunosuppressive effect. The significance of the immunomodulatory effect of morphine is discussed in this report.
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PMID:Enhancement of tumor growth by morphine and its possible mechanism in mice. 822 Mar 22

Detection of interleukin (IL)-1 activity was studied in two human bladder cancer cell lines, T24 and EJ1, and one rat bladder carcinoma cell line, 804G. Significantly high proliferation of mouse thymocytes in the assay of IL-1 activity was observed in the conditioned medium (CM) of T24 cells, indicating that the cells released IL-1-like activity. Enzyme-linked immunosorbent assay (ELISA) and Northern blot analysis showed the presence of both IL-1 alpha and IL-1 beta in the CM of T24 cells and expression of mRNAs of both cytokines in the cells. Interleukin-1 activity in EJ1 cells, which produced a little activity, was induced by E. coli lipopolysaccharide (LPS) while it was not induced in T24 by either LPS or other test substances. Conditioned medium of T24 increased proliferation of both T24 and EJ1 in cell-growth assay. Further investigation of the mode of action and role of cytokines, especially those from tumor cells themselves, is necessary in relation to BCG or photodynamic therapy.
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PMID:Detection of interleukin-1 activity in human bladder cancer cell lines. 830 99

We looked for chemotaxin/interleukin 8 (CT/IL-8) activity in the culture fluids of 97 human leukemia cell lines and found it in two of the T cell lines, six of the myeloid cell lines, and one of the normal B-cell lines. It was particularly strong in the culture fluids of two cell lines. These cell lines secreted a chemotactic protein into the culture fluids under certain conditions of stimulation with phorbol-12-myristate 13-acetate (PMA), lipopolysaccharide, or hemagglutinin-P. A myeloid leukemia cell line, ML-1, secreted an inducible chemotaxin when stimulated with PMA (1 ng/ml) for 24 h. We purified the chemotaxin from ML-1 cell culture fluid using an improved procedure: concentration with DEAE-Sepharose CL-6B and CM-Sepharose CL-6B, CM-Sepharose column chromatography, and reverse-phase 5TMS-300 column on HPLC with the retention time coinciding with that of LUCT/IL-8 [Suzuki et al., 1989, J. Exp. Med. 169, 1895]. The yield was 200 micrograms protein from 6 liters of the culture fluid. The N terminus of CT/IL-8 was AVLPR-SAKELRXQXIKTYSK- - -, the same as that of LUCT/IL-8, which is constitutively secreted from lung giant cell carcinoma LU65C cells. The optimal concentration in the chemotactic activity of CT/IL-8, equivalent to that of bacterial chemotactic peptide fMet-Leu-Phe (10 nM), was found to be 5 nM. The results show that this chemotaxin is identical to LUCT/IL-8.
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PMID:Isolation and amino acid sequence of a chemotactic protein, LECT/interleukin 8, from a human myeloid leukemia cell line, ML-1. 834 17

Neutrophils are important cellular mediators in inflammatory bowel disease (IBD). Interleukin (IL)8, a powerful neutrophil chemoattractant, is found in increased quantities in inflamed mucosa, but the cells of origin are uncertain. IL8 gene expression was studied by in situ hybridisation in uninflamed intestinal tissue resected for colon carcinoma (n = 7) and in inflamed colonic tissue resected for IBD (n = 11). Immunohistochemistry was used to assess the phenotype of IL8 expressing macrophages and the production of IL8 protein. Macrophages isolated from intestinal resections and lipopolysaccharide stimulated peripheral blood monocytes treated with 5-aminosalicylic acid, hydrocortisone, and cyclosporin A were examined for IL8 mRNA by northern blotting and IL8 secretion by enzyme linked immunosorbent assay (ELISA). In all cases IL8 mRNA was detected by in situ hybridisation in macrophages and neutrophils adjacent to ulceration in inflamed bowel, but not detected in uninflamed mucosa from carcinoma resections. Recently recruited CD14 positive macrophages were responsible for some of this IL8 expression. IL8 protein was present in the same distribution as mRNA. Epithelial cells in normal and inflamed tissue showed neither mRNA nor protein. IL8 mRNA was expressed significantly more commonly by macrophages from IBD affected than from normal mucosa, and IL8 secretion by IBD but not normal colon macrophages was augmented significantly by lipopolysaccharide treatment. IL8 expression and production by lipopolysaccharide treated blood monocytes was inhibited by the therapeutic agents tested. These results show that neutrophils and recently recruited macrophages are responsible for production of IL8 in IBD, suggesting a mechanism for a continuing cycle of neutrophil attraction. Agents used therapeutically in these diseases may be effective in part by disrupting this cycle.
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PMID:Interleukin 8: cells of origin in inflammatory bowel disease. 856 66

Taxol is important in the treatment of both primary and drug-resistant ovarian cancer. Although Taxol is known to stabilize microtubules and block cell mitosis, the effectiveness of this drug exceeds that of other antimitotic agents, suggesting it may have an additional mode of action. Stimulated by murine macrophage studies indicating cytokine induction by Taxol, we have investigated proinflammatory cytokine expression in a series of cell lines and recent explants of human ovarian cancer. Taxol induced secretion of interleukin (IL) 8 but not IL-6, IL-1alpha, or IL-1beta in 4 of 10 samples. Induction was dependent on transcriptional activation, and, in contrast to murine macrophage studies, was apparently independent of an active lipopolysaccharide signaling pathway. Confluent cultures secreted as much IL-8 as proliferating cells. Taxol did not induce IL-8 in breast carcinoma, endometrial stromal, or T-lymphocyte or monocyte cultures. We propose that the local expression of this chemokine in vivo may elicit a host response similar in effectiveness to that of cytokine gene therapy. These data are the first to suggest that a chemotherapeutic agent may have a direct effect on transcription of cytokine and/or growth factor genes in ovarian cancer, and that this effect may not be restricted to proliferating tumor cells.
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PMID:Taxol-dependent transcriptional activation of IL-8 expression in a subset of human ovarian cancer. 864 Aug 18

Calcitonin gene-related peptide (CGRP) inhibits antigen presentation by Langerhans cells (LC) and macrophages, and LC are anatomically associated with CGRP-containing epidermal nerves. To determine whether CGRP may produce some of its functional effects through regulation of cytokine expression, we utilized enzyme-linked immunosorbent assay (ELISA) of conditioned supernatants to examine production of interleukin (IL)-10 and IL-1 beta protein in the LC-like cell line XS52 as well as the reverse transcriptase-polymerase chain reaction (RT-PCR) to examine levels of mRNA for IL-10, IL-1 beta, and the 40-kDa subunit (p40) of IL-12. CGRP augmented the lipopolysaccharide (LPS) and granulocyte-macrophage colony-stimulating factor (GM-CSF) -induced release of IL-10 protein and the induced expression of IL-10 mRNA in these cells. However, it suppressed the induction of release of IL-1 beta protein and the induction of mRNA for IL-12 p40 and IL-1 beta by LPS and GM-CSF. Regulation of cytokine expression in peritoneal macrophages was also examined. By ELISA, the LPS-induced expression of IL-10 was augmented by CGRP, whereas the induction of IL-1 beta was suppressed. Northern analysis demonstrated augmentation of LPS-induced IL-10 mRNA levels and inhibition of LPS-induced IL-1 beta mRNA by CGRP. CGRP inhibited the LPS-induced induction of IL-12 mRNA as assessed by RT-PCR. Up-regulation of B7-2 expression by LPS and GM-CSF was suppressed by CGRP in both XS52 cells and macrophages, as previously reported. This suppression, however, could be abrogated by co-culture with neutralizing antibodies to IL-10. Furthermore, the presence of neutralizing antibodies to IL-10 during exposure of epidermal cells (EC) to CGRP prevented the CGRP-mediated suppression of EC presentation of tumor-associated antigens (from the S1509a spindle cell carcinoma) for elicitation of delayed-type hypersensitivity in S1509a-immune mice. These data suggest that suppression of antigen-presenting function by CGRP is mediated, at least in part, by changes in cytokine expression that favor less robust antigen presentation for cell-mediated immunity.
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PMID:Regulation of cytokine expression in macrophages and the Langerhans cell-like line XS52 by calcitonin gene-related peptide. 902 28

The cytotoxicity and immunosuppressive activities of jaborosalactone-L and three 16 alpha-oxygenated withanolides from the leaves of Discopodium penninervium were studied. Jaborosalactone-L showed cytotoxicity only to the murine macrophage cell line, RAW 264.7, but the 16 alpha-oxygenated withanolides exhibited cytotoxicity to both human (COR-L23 and ECV 304) and murine (L929 and RAW 264.7) carcinoma cell lines with IC50 values ranging from 1.2-150 microM. The non-toxic concentrations of these withanolides were also found to reduce the proliferative response of both inactive and E. coli lipopolysaccharide and concanavalin A activated rat spleen cells in vitro.
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PMID:Cytotoxicity and immunosuppressive activity of withanolides from Discopodium penninervium. 906 90

Matrilysin is a matrix metalloprotease that is overexpressed in cancer cells of epithelial origin and in normal tissues during events involving matrix remodeling such as the cycling endometrium. We previously observed that inflamed ductule and acinar epithelia in the prostate also overexpress matrilysin. The presence of infiltrating macrophages in these areas prompted us to determine if factors secreted from monocytes could induce matrilysin expression in a human prostatic cell line. Conditioned media collected from the monocyte cell line THP-1 following lipopolysaccharide treatment substantially induced matrilysin protein and mRNA expression in LNCaP prostate carcinoma cells. Matrilysin expression in LNCaP cells was also induced by recombinant interleukin (IL)-1 (50 pM), but not by equimolar concentrations of recombinant tumor necrosis factor-alpha or IL-6. The matrilysin-inducing activity of THP-1 conditioned medium was completely abrogated by preincubation with a neutralizing antibody to IL-1beta. Transient transfection analyses with a chimeric human matrilysin promoter-chloramphenicol acetyltransferase reporter construct demonstrated that IL-1beta activates transcription through the matrilysin promoter in LNCaP cells. This is the first report of matrilysin induction by an inflammatory cytokine in a cell line of epithelial origin, and the results suggest a potential mechanism for the overexpression of matrilysin in inflamed ducts and glands of the prostate.
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PMID:Interleukin-1beta secreted from monocytic cells induces the expression of matrilysin in the prostatic cell line LNCaP. 916 49


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