Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have shown recently that normal human mammary epithelial cells do produce interleukin 6 (IL6), interleukin 8, and a nonsecreted form of tumor necrosis factor. Here we report that ductal infiltrating mammary carcinomas fail to express immunoreactive IL6. Since abnormalities of cytokine genes are a frequent event in cancer, we investigated the production of and the response to cytokines of mammary cells using a panel of oncogene-transformed cells derived from the spontaneously immortalized MCF-10A cell line. We found that only the parental line and the int-2-transformed cells responded to exogenous IL6 and/or were suppressed by IL6-neutralizing antibody. In contrast to highly transformed cells, these two lines, which were either nontransformed (MCF-10A) or weakly transformed (int-2), were found to express IL6 receptors. These data suggest that loss of IL6 pathways can be a marker of mammary cell transformation.
Cancer Res 1993 Jul 01
PMID:Growth-stimulating activity of interleukin 6 on human mammary epithelial cells transfected with the int-2 gene. 810 Apr 82

Induction of IL-8 gene expression was investigated in IL-2-stimulated circulating peripheral blood polymorphonuclear neutrophils (PMN). Brief exposure of normal PMN to human rIL-2 enhanced both transcriptional and translational expression of IL-8. The IL-8 mRNA was first detectable by 3 h, followed by a continuous maintenance of high mRNA levels up to 18 h. Maximal transcription was obtained with 1000 U/ml of IL-2, which achieved the level observed with known neutrophil-activating factors such as granulocyte macrophage-CSF and Candida albicans. The protein synthesis inhibitor, cycloheximide, had no detectable effect on levels of IL-8 mRNA expression in PMN incubated in medium alone; however, cycloheximide could selectively modulate IL-8 mRNA transcription in PMN, depending on the cytokine used. Cycloheximide did not affect or alter IL-8 mRNA induction in IL-2-treated PMN but abrogated it in granulocyte macrophage-CSF-treated PMN and super-induced the level of IL-8 mRNA in C. albicans-treated PMN. Of significance was the observation that IL-2 has no direct chemotactic effect on PMN, whereas the cell-free supernatants from IL-2-stimulated PMN show potent chemotaxis for freshly isolated PMN, which can be specifically blocked by anti-IL-8 Abs. These findings suggested that the induction of IL-8 gene expression in PMN by IL-2 may be involved in the recruitment of PMN into tissues during local IL-2 therapy in human cancer and in part contribute to tumor rejection.
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PMID:Induction of IL-8 gene expression in human polymorphonuclear neutrophils by recombinant IL-2. 814 38

We correlated the steady state transcription and protein secretion of interleukin 8 (IL-8) in 13 different human melanoma cell lines with their ability to grow and produce metastasis in nude mice. Highly metastatic cells expressed higher steady state levels of IL-8 mRNA transcripts than did low metastatic cells. In situ mRNA hybridization analyses confirmed the pattern of mRNA expression on a cellular level. Increased mRNA expression directly correlated with secretion of IL-8 protein as determined by enzyme-linked immunosorbent assay. Recombinant IL-8 stimulated the proliferation of low metastatic A375P cells in a dose-dependent manner, a stimulation that was abrogated by the use of a polyclonal antibody against IL-8. The data suggest that IL-8 can be an autocrine growth factor for human melanoma cells and that IL-8 is involved in melanoma metastasis.
Cancer Res 1994 Jun 15
PMID:Expression of interleukin 8 correlates with the metastatic potential of human melanoma cells in nude mice. 820 46

Liposomal muramyl tripeptide phosphatidylethanolamine (L-MTP-PE) is a biological agent in phase I and II trials for osteosarcoma and melanoma. Its mechanism of action has been linked to its ability to activate monocyte tumoricidal function and to stimulate monocyte production of tumor necrosis factor (TNF) and interleukins(IL)-1, -6, and -8. Our ultimate goal is to combine L-MTP-PE with chemotherapy. The purpose of this study was to determine whether doxorubicin (Adriamycin) interfered with the ability of L-MTP-PE to activate monocyte cytokine production. Human monocytes were cultured with or without 5-500 ng/ml of Adriamycin for 3 h and washed before being exposed to 2 micrograms/ml L-MTP-PE for 16 h. Cultured supernatants were collected and assayed for TNF, IL-1, IL-6, and IL-8. The messenger RNA expression of IL-1 alpha, IL-1 beta, TNF alpha, IL-6, and IL-8 was quantified with northern blot analysis. Adriamycin did not suppress the up-regulation of any of these cytokines. We concluded that combination therapy with L-MTP-PE and Adriamycin is feasible and that this combination warrants further investigation in a clinical setting.
Cancer Immunol Immunother 1993 Nov
PMID:Effect of Adriamycin on liposomal muramyl tripeptide's ability to up-regulate monocyte cytokine expression. 824 65

Virtually pure primary cultures of normal mammary epithelial cells (MEC) obtained from healthy women were shown to release interleukin 6 and 8 (IL6, IL8) and to produce a nonsecreted form of tumor-necrosis factor (TNF). No interferon (IFN), whether alpha, beta, or gamma, or IL1-alpha or -beta could be detected. Analysis of cellular RNA confirmed these findings and showed that MEC also express IL6 receptor and TNF-alpha-related mRNAs. Epithelial cells were selectively stained by antibodies to IL6, IL8 and TNF-alpha both in primary cultures and in the normal mammary gland. Samples of human milk contained sizable amounts of IL6, IL8 and IFN-gamma; yet the liquid phase was consistently negative for other cytokines (i.e., TNF-alpha, IFN-alpha/-beta, IL1-alpha/-beta). Expression of IL6 (but not of IL8 and TNF-alpha) was abolished in ductal infiltrating carcinomas and greatly reduced in cultures of oncogene-transfected mammary cells, suggesting that alterations of IL6 expression are associated with pathogenesis in breast cancer.
Int J Cancer 1993 Dec 02
PMID:Normal breast epithelial cells produce interleukins 6 and 8 together with tumor-necrosis factor: defective IL6 expression in mammary carcinoma. 825 29

Liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (L-MTP-PE), a new biologic response modifier, was designed to target the immunomodulator to monocytes and macrophages. Human monocytes/macrophages phagocytize L-MTP-PE, with subsequent upregulation of interleukin (IL)-1 alpha, IL-1 beta, IL-6, IL-8, tumor necrosis factor (TNF)-alpha, and monocyte chemotactic and activating factor genes and with the production and secretion of these cytokines in vitro. L-MTP-PE-activated macrophages kill tumor but not normal cells in vitro. Following i.v. infusion of L-MTP-PE into cancer patients, its uptake was demonstrated in liver, spleen, lung, and in and around metastases to lung. We also investigated whether L-MTP-PE therapy administered in a neoadjuvant setting could improve the disease-free interval in relapsed osteosarcoma patients with lung metastasis. Patients received either a 12- or 24-week course of L-MTP-PE after surgical removal of all metastases. Following L-MTP-PE infusion, induction of circulating TNF-alpha, IL-6, neopterin, and C-reactive protein was demonstrated. Disease-free intervals were calculated from the day of surgery to the day of relapse in each group and were compared with the disease-free interval for a historical control group. Those patients receiving 24 weeks of L-MTP-PE showed a significant (p < 0.03) prolongation in time to relapse. These data indicate that L-MTP-PE is an active agent against osteosarcoma and warrants further investigation in an adjuvant setting.
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PMID:Liposome-encapsulated MTP-PE: a novel biologic agent for cancer therapy. 828 Jul 10

This review concentrates on growth autonomy of tumor cells in relation to tumor progression. Human malignant melanoma serves as an example for progressive growth factor independence at subsequent stages of tumor progression. Mechanisms by which malignant cells acquire growth factor independence are discussed. In melanoma, deregulation of growth regulatory pathways has been described on four levels: 1) aberrant production of autocrine growth factors that substitute for exogenous growth factors (basic fibroblast growth factor [bFGF]); 2) alterations in the response to negative autocrine growth factors (interleukin [IL]-6 and transforming growth factor [TGF]-beta); 3) overexpression of epidermal growth factor receptors (EGF-R); and 4) alterations of cellular protooncogenes involved in signal transduction (RAS, MYB) and growth suppression (p53). In addition to bFGF and IL-6, multiple other growth factor genes are activated in malignant melanoma cells but not normal melanocytes. These include both chains of platelet-derived growth factor (PDGF), TGF-alpha, IL-1, IL-8, and tumor necrosis factor (TNF)-alpha. Of these, PDGF-B has been investigated in more detail. Melanoma-derived PDGF clearly does not act in a direct autocrine mode, but has important paracrine effects on normal tissue constituents, notably fibroblasts and endothelial cells, that are essential for tumor development in vivo. It is speculated that other melanoma-derived growth factors with as yet undefined functions similarly exert such paracrine or 'indirect' autocrine effects that cannot be sufficiently addressed in studies on cultured cells.
Cancer Metastasis Rev 1993 Sep
PMID:Growth factor independence and growth regulatory pathways in human melanoma development. 828 9

Interleukin-8 (IL-8) has been recently shown to bind to human erythrocytes with high affinity and is therefore potentially difficult to detect in serum or plasma. IL-8 is transiently elevated in the serum of baboons after the administration of interleukin-1 alpha (IL-1 alpha). The objective of this study was to investigate whether IL-8 can be detected in the plasma or in detergent-lysed erythrocytes from cancer patients undergoing treatment with IL-1 alpha. Using a specific radioimmunoassay (RIA), plasma IL-8 was detected within 1-2 h after the first IL-1 alpha infusion. Thereafter, the levels declined rapidly and after 4-8 h were undetectable. Erythrocyte-bound IL-8 was detectable 1-2 h after the increase in plasma levels. The erythrocyte-bound IL-8 levels were higher than those measured in plasma and remained elevated long after the plasma levels had become undetectable. Erythrocyte membranes accounted for all of the erythrocyte-associated IL-8, as IL-8 was undetectable in the cytosol after erythrocyte lysis. The assay used in these studies detects IL-8 in erythrocyte lysates when it cannot be measured in plasma and may therefore be useful in monitoring IL-8 production in vivo.
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PMID:A method for the detection of erythrocyte-bound interleukin-8 in humans during interleukin-1 immunotherapy. 835 94

The clinicopathological features of malignant cells are sometimes modified by autologous cytokine production. Inflammatory fibrous histiocytoma (IFH) is characterised by leukocyte infiltration and is a variant of malignant fibrous histiocytoma (MFH). We demonstrated that three MFH cell lines (MF-1, MF-3, and MF-4) have the potential to promote neutrophil chemotaxis and to express mRNA for the cytokines, granulocyte-macrophage colony stimulating factor (GM-CSF) and/or interleukin 8/neutrophil attractant/activation protein 1 (IL-8/NAP-1), both with and without interleukin 1 beta (IL-1 beta) stimulation. MF-1 cells showed the spontaneous production of neutrophil chemotactic activity and the expression of both of GM-CSF and IL-8/NAP-1 mRNA, which was enhanced by exogenous IL-1 beta. In contrast, MF-3 cells showed the expression of GM-CSF and IL-8/NAP-1 mRNA with IL-1 beta stimulation but not without it, and MF-4 cells expressed only IL-8/NAP-1 mRNA when stimulated with IL-1 beta (time- and dose-dependent expression). These findings suggest that neutrophil chemotactic cytokines derived from IFH cells might be responsible for the prominent infiltration of neutrophils in this disease.
Br J Cancer 1993 Mar
PMID:Neutrophil chemotactic factors produced by malignant fibrous histiocytoma cell lines. 838 9

Bacterial superantigens are the most potent known activators of human T lymphocytes. To engineer superantigens for immunotherapy of human colon carcinoma, the superantigen, staphylococcal enterotoxin A (SEA) was genetically fused to the Fab region of the colon carcinoma-reactive monoclonal antibody C242. In the present study the effector mechanisms involved in the anti-tumor response to C242 Fab-SEA were characterized. Immunohistochemistry and computer-aided image analysis were used in studies of cryopreserved tumor tissue to evaluate the phenotype of infiltrating cells and their cytokine profiles in response to therapy. Human T cells and monocytes were recruited to the tumor area and penetrated the entire tumor mass within hours after injection of C242 Fab-SEA. The production of cytokines at the single-cell level was found to be dominated by tumor necrosis factor (TNF)-alpha, interleukin (IL)-2, IL-4, IL-5, IL-10, IL-12, interferon (IFN)-gamma, granulocyte-macrophage colony-stimulating factor, and transforming growth factor-beta, whereas IL-1-alpha, IL-1ra, IL-1 beta, TNF-beta, IL-3, IL-6, and IL-8 were undetectable. Most of the TNF-alpha, IL-2, IL-12, and IFN-gamma were made by the infiltrating human leukocytes, while the colon carcinoma cells were induced to produce IL-4, IL-10, and TNF-alpha. Up-regulation of IFN-gamma receptors and TNF R p60 receptors was found, while the TNF R p80 receptor was absent. The cytokine production, T cell infiltration, and CD95 Fas receptor expression concomitantly occurred to induce programmed cell death in the tumor cells. This was followed by a strong reduction of the tumor mass that was seen within 24 h after C242 Fab-SEA infusion. These findings demonstrate that antibody-superantigen proteins efficiently recruit tumor-infiltrating lymphocytes actively producing a variety of cytokines likely to be essential for the therapeutic effects observed in the model. Although the humanized SCID model has obvious limitations in its predictive value for treatment of human cancer, we believe that these results encourage clinical evaluation of antibody-targeted superantigens.
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PMID:Antibody-targeted superantigen therapy induces tumor-infiltrating lymphocytes, excessive cytokine production, and apoptosis in human colon carcinoma. 856 49


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