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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ovarian surface epithelium (OSE) takes part in the lysis and repair of the ovulatory site. It also forms invaginations and cysts that give rise to the majority of ovarian epithelial carcinomas. In the present study, we investigated the capacity of cultured human OSE to secrete cytokines that may contribute to the regulation of ovarian functions and may influence ovarian carcinogenesis. Bioassays, combined with antibody neutralization experiments, showed that OSE cells in short-term culture secrete bioactive interleukin-1 (IL-1), interleukin-6 (IL-6), macrophage colony-stimulating factor (CSF-1), granulocyte colony-stimulating factor (G-CSF), and limited granulocyte-macrophage colony-stimulating factor (GM-CSF). There was a tendency for these factors to be absent or secreted in reduced amounts in SV40-immortalized OSE lines and in two ovarian carcinoma lines. No IL-2, IL-3, or IL-4 was detected. The results show that normal OSE cells secrete factors that are known to have regulatory effects on follicular growth and differentiation, ovulation, and the distribution of intraovarian cells of the immune system. In addition, the results suggest that the secretion of cytokines by ovarian carcinomas represents the retention of normal precursor cell properties, rather than new characteristics acquired as a result of neoplastic progression.
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PMID:Secretion of bioactive interleukin-1, interleukin-6, and colony-stimulating factors by human ovarian surface epithelium. 769 Nov 94

Recent reports imply that several epidermal cytokines have a functional role in the tumor promotion stage of the multistage carcinogenesis model in mouse dorsal skin. In this report we describe studies to assess the role of interleukin-6 (IL-6) in tumor promotion. Promoting, as well as non-promoting, hyperplastic agents were found to induce IL-6, as measured by mRNA expression. Inhibitors of tumor promotion inhibited tumor-promoter-mediated IL-6 induction. However, when mice were injected with a neutralizing antibody specific to murine IL-6, there was no effect on tumor-promoter-mediated epidermal hyperplasia and dermal inflammation. These studies suggest that even though IL-6 is produced in the epidermis following tumor promoter application, it does not modulate epidermal hyperplasia and dermal inflammation. Our findings also stress the importance of assessing, in in vivo studies, the function of those cytokines suggested by in vitro experiments to have important roles in tumor promotion.
Carcinogenesis 1994 Aug
PMID:Induction of interleukin-6 in the epidermis of mice in response to tumor-promoting agents. 805 55

Interleukin-6 (IL-6) is a pleiotropic cytokine that is not only a mediator in major immunologic reactions but also a growth factor of keratinocytes. We studied the IL-6 secretion in vitro of 15 human cell lines derived from both squamous cell carcinoma (SCC) and adenocarcinoma of the uterine cervix. Four of the eight well differentiated SCC secreted a large amount (> 1500 pg/48 h/10(6) cells) of IL-6 in nude mice. In contrast, poorly differentiated SCC cell lines and all of the 7 adenocarcinoma cell lines secreted a small amount (< 500 pg/48 h/10(6) cells of IL-6). The expression of IL-6 mRNA of the cell lines correlated well with their IL-6 secretion potential. However, the expression of IL-6 receptor did not correlate with the IL-6 secretory potential. We also studied the IL-6 secretion of freshly isolated normal squamous epithelium and of dysplastic epithelium. In culture, two normal squamous epithelia secreted a large amount (> 2000 pg/48 h/10(6) cells), whereas 8 dysplasia epithelia secreted an extremely small amount (< 10 pg/48 h/10(6) cells). About one-third of patients with SCC had a raised serum IL-6 value. IL-6 production may help to differentiate between SCC and adenocarcinoma of the uterine cervix. IL-6 regulation seems to change in the course of SCC carcinogenesis.
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PMID:Interleukin-6 (IL-6) production in carcinoma of the cervix. 878 30

Since the enhanced production of IL-10 by human bronchogenic carcinoma has already been documented, in the present study serum levels of IL-10 were measured serially in patients with lung cancer undergoing radiotherapy. Thirty-one full diagnosed cancer patients underwent the radiotherapy procedures. The interleukin-10 (IL-10) and interleukin-6 (IL-6) serum levels were measured before therapy and after 3, 6 and 12 months after therapy. The interleukins concentrations were evaluated using a solid phase sandwich Enzyme-Linked-Immuno-Sorbent-Assay (ELISA). In all patients the serum levels of IL-10 have been found elevated. Due to the treatment they progressively declined to almost normal ranges in responders, while they remained elevated in non-responders. Serum levels of interleukin-6 have been elevated in the majority of our patients. After 12 months observation they also decreased, mainly in patients responding to the treatment. No correlation between serum IL-10 and IL-6 level has been found. The importance of serum IL-6 determination in lung cancer patients monitoring has already been established. The present study shows, that in spite of still unclear role of IL-10 in the process of carcinogenesis, it may be considered as a prognostic factor in lung cancer.
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PMID:Serum levels of interleukin-10 and interleukin-6 in patients with lung cancer. 884 1

The differential display technique was used to identify genes whose expression was regulated by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Expression of a novel sequence was up-regulated in a dose-dependent fashion in liver of Sprague-Dawley male rats exposed to both chronic and acute treatment with TCDD, as measured by densitometry of Northern blot analyses (P < 0.01). A rapid amplification of cDNA ends (RACE) procedure was used to isolate a 1.8 kb cDNA from a rat liver cDNA preparation. This cloned cDNA, called 25-Dx, was sequenced and found to encode a peptide of 223 amino acids. In control rats, the 25-Dx gene was expressed at high levels in lung and liver. A hydrophobic domain of 14 residues followed by a proline-rich domain, both located in the N-terminal region, showed 71% homology with the transmembrane domain of the precursor for the interleukin-6 receptor and a conserved consensus sequence found in the cytokine/growth factor/prolactin receptor superfamily respectively.
Carcinogenesis 1996 Dec
PMID:Isolation and characterization of a novel gene induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in rat liver. 900 96

Hydrogen peroxide (H2O2) and some cytokines that are released during the inflammatory process are important factors for the development of urinary bladder carcinoma and for its growth. Sustained induction of H2O2-generating peroxisomal fatty acyl-CoA oxidase (ACOX) in the liver of rats and mice by non-genotoxic peroxisome proliferators leads to the development of liver tumors. To examine the role of intracellular H2O2 generated by ACOX during urinary bladder carcinogenesis, we overexpressed rat ACOX in a non-tumorigenic rat urothelial cell line, MYP3, under the control of the cytomegalovirus promoter. The clones overexpressing rat ACOX, when exposed to a fatty-acid substrate (150 microM linoleic acid), demonstrated strikingly higher levels of intracellular H2O2 (p > 0.001) and formed colonies in soft agar in proportion to the duration of exposure to linoleic acid. Furthermore, all the transformants, which were selected at random from soft agar, demonstrated an accelerated growth potential on a plastic surface, as well as tumorigenicity in athymic nude mice. In addition, the growth of these transformants was stimulated by cytokines, interleukin-6 and tumor necrosis factor-alpha, better than the growth of ACOX-overexpressing, but non-transformed cells or that of the parental cells. Our results clearly demonstrate that H2O2 induced by ACOX acts as a carcinogen on urothelial cells, and that transformed cells have acquired an advantage for growth over nonneoplastic cells because of their selective response to the stimulatory action of several cytokines.
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PMID:Tumorigenic conversion of a non-tumorigenic rat urothelial cell line by overexpression of H2O2-generating peroxisomal fatty acyl-CoA oxidase. 909 54

Activator protein-2 is an important transcription factor for the activation of a number of genes. Here we report the induction of activator protein-2 in response to inflammatory cytokines such as interleukin-6 in keratinocytes. Immunoblotting and semiquantitative reverse transcriptase-polymerase chain reaction assays using normal human keratinocytes revealed that interleukin-6 caused a time- and concentration-dependent induction of activator protein-2 mRNA and protein. The increase of activator protein-2 mRNA was detected at 30 min after stimulation and that of activator protein-2 protein was at 2 h. Their levels were lower than the control levels at 24 h. The interleukin-6-dependent induction of activator protein-2 mRNA was completely blocked by adding actinomycin D, whereas it was approximately 50% affected by cycloheximide. Co-incubation with neutralizing antibodies against various inflammatory cytokines resulted in inhibition of the interleukin-6-dependent activator protein-2 induction at varying degrees, indicating an involvement of various cytokines in the activator protein-2 induction. The activator protein-2 induction was observed in keratinocytes derived from lesional skins with psoriasis or squamous cell carcinoma, and the high levels of activator protein-2 were histochemically detected in these lesions. Furthermore, a gel mobility shift assay using the nuclear extracts from interleukin-6-treated cells showed that interleukin-6 induced the functional activator protein-2 protein for the gene activation. These findings suggest a possible regulation mechanism of activator protein-2 through a complex cytokine system, which is conceivably the initial reaction leading to skin inflammation, and resultant keratinocyte growth and carcinogenesis.
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PMID:Induction of transcription factor AP-2 by inflammatory cytokines in human keratinocytes. 1050 47

Cyclooxygenase (COX)-2 levels are elevated in several types of human cancer tissues. Nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit both the COX-1 and COX-2 protein, the two enzymes that convert arachidonic acids to prostaglandins. Regular use of such NSAIDs significantly reduces the risk and spread of some cancers. The objective of this study was to elucidate the molecular pathology of neoplasms that overexpress COX-2. Epidemiological data and clinical studies were analyzed and compared with results of studies of human tumor tissues, animal models, and cultured tumor cells. COX-2, but not COX-1, is highly expressed in human colon carcinoma, squamous cell carcinoma of the esophagus, and skin cancer. COX-2 is inducible by oncogenes ras and scr, interleukin-1, hypoxia, benzo[a]pyrene, ultraviolet light, epidermal growth factor, transforming growth factor beta, and tumor necrosis factor alpha. Dexamethasone, antioxidants, and tumor-suppressor protein p53 suppress COX-2 expression. COX-2 synthesizes prostaglandin E2 (PGE2) which stimulates bcl-2 and inhibits apoptosis, and induces interleukin-6 (IL-6) which enhances haptoglobin synthesis. PGE2 is associated with tumor metastases, IL-6 with cancer cell invasion, and haptoglobin with implantation and angiogenesis. Drastic reduction in polyp number results from COX-2 gene knockout as well as from selective COX-2 inhibition in a mouse model of human familial adenomatous polyposis. Nonselective NSAIDs, for instance aspirin, and selective COX-2 inhibitors such as celecoxib (SC-58635) and NS-398 suppress azoxymethane-induced colon carcinogenesis in rats. Aspirin, indomethacin, and ibuprofen decrease cultured lung cancer cell proliferation. Selective inhibition of COX-2 is preferable to nonselective inhibition. It reduces cancer cell proliferation, induces cancer cell apoptosis, and spares COX-1-induced cytoprotection of the gastrointestinal tract.
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PMID:Molecular pathology of cyclooxygenase-2 in neoplasia. 1067 79

We have compared the induction of apoptosis and cytokine release by UVB and gamma-radiation in primary (untransformed) and in two immortalized human epithelial/keratinocyte cell lines, HaCaT and KB (KB is now known to be a subline of the ubiquitous keratin-forming tumour cell line HeLa and we therefore designate it HeLa-KB). In both the primary and the immortalized cell lines apoptosis and release of the inflammatory cytokine interleukin-6 are induced rapidly following UVB irradiation. In contrast, only the immortalized cells undergo apoptosis and release interleukin-6 after gamma-irradiation and here the onset of apoptosis and cytokine release are delayed. The same distinction between primary and immortalized cells was observed when double-strand breaks were induced with the anticancer drug mitoxantrone, which stabilizes topoisomerase II-cleavable complexes. We suggest that immortalization may sensitize keratinocytes to the apoptogenic effect of ionizing radiation or mitoxantrone by deregulating normal cell cycle checkpoints. In both human keratinocytes and fibroblasts, cell killing, as assayed by loss of colony-forming ability, is not coupled to apoptosis. Immortalization increases resistance to gamma-radiation killing but sensitizes to apoptosis. In contrast, although immortalization also sensitizes to UVB-induced apoptosis, it does not affect UVB-induced cell killing. Apoptosis unambiguously indicates death at the single cell level but clonal cell survival integrates all the cellular and genetic processes which prevent or permit a scorable clone to develop.
Carcinogenesis 2000 Jun
PMID:Apoptosis and cytokine release induced by ionizing or ultraviolet B radiation in primary and immortalized human keratinocytes. 1083 95

In a previous paper [Lim, Park, Jee, Lee and Paik (1999) J. Cancer Res. Clin. Oncol. 125, 493-499], we showed two major forms of active DNA-6-O-methylguanine:protein-L-cysteine S-methyltransferase (MGMT; EC 2.1.1.63) in the liver with N-nitrosodiethylamine (DEN)-induced carcinogenesis: these were 26 and 24 kDa species. Here we show that a 2 kDa C-terminal fragment was cleaved from the 26 kDa species in vitro by thrombin or microsomal fractions isolated from DEN-treated rat livers. When Ser(204) of the 26 kDa protein was replaced with Ala by site-directed mutagenesis, phosphorylation of the protein was completely abolished, indicating Ser(204) to be the site of phosphorylation. We also show that the phosphorylation was performed by Ca(2+)-independent protein kinase isoenzymes, and that the phosphorylated rat MGMT protein was resistant to digestion by protease(s) whose activity was increased during DEN-induced hepatocarcinogenesis and also by digestion with endopeptidase Glu-C (V8 protease).
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PMID:Phosphorylation of methylated-DNA-protein-cysteine S-methyltransferase at serine-204 significantly increases its resistance to proteolytic digestion. 1110 89


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