Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin-6 (IL-6) is produced at high levels by renal cell carcinoma cell lines. The molecular mechanisms involved in its possible role as an autocrine growth factor were investigated. IL-6 and IL-6 receptor expression was investigated in 8 renal cell carcinoma (RCC) cell lines. The modulation of RCC cell line proliferation by an anti-IL-6 Ab, an IL-6 antisense oligonucleotide (ASON) directed against the second exon of IL-6 and cytokines inhibiting IL-6 production (IL-4 and IL-13) was investigated. All 8 RCC cell lines expressed IL-6 mRNA, produced IL-6 and expressed the soluble and membrane-bound gp130 chain of IL-6 receptor. The gp80 chain of IL-6 receptor was undetectable at the surface of the 8 RCC cell lines tested, while the soluble form of gp80 was detectable in the supernatant of one of these cell lines. The addition of a blocking IL-6 Ab did not inhibit the proliferation of any of the 8 RCC cell lines. In contrast, IL-6 ASON inhibited specifically IL-6 production and the proliferation of all RCC cell lines. Exogenous IL-6 failed to restore RCC cell line proliferation blocked by ASON, indicating that IL-6 acts through an intracrine loop in RCC cell lines. IL-13 and IL-4 inhibited the proliferation of 7 of the 8 cell lines without interfering with IL-6 or IL-6 receptor expression. IL-6 ASON inhibited the proliferation of the 8 RCC cell lines tested additively with IL-4 or IL-13. IL-6 is an intracrine growth factor in renal cell carcinoma cell lines.
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PMID:IL-6 as an intracrine growth factor for renal carcinoma cell lines. 1525 33

Human plasma membrane-associated sialidase (NEU3), specifically hydrolyzing gangliosides, plays crucial roles in the regulation of cell surface functions. Here we demonstrate that NEU3 mRNA level are increased in renal cell carcinomas (RCCs) compared with adjacent non-tumor tissues, significantly correlating with elevation of interleukin-6 (IL-6), a pleiotropic cytokine that has been implicated in immune responses and pathogenesis of several cancers, including RCCs. In human RCC ACHN cells, IL-6 treatment enhanced NEU3 promoter luciferase activity 2.5-fold and the endogenous sialidase activity significantly. NEU3 transfection or IL-6 treatment resulted in both suppression of apoptosis and promotion of cell motility, and the combination had synergistic effects. NEU3 scarcely affected MAPK- or IL-6-induced STAT3 activation but promoted the phosphatidylinositol 3-kinase (PI3K)/Akt cascade in both IL-6-dependent and -independent ways. Consistent with these data, NEU3 markedly inhibited staurosporine-induced caspase-3 activity and enhanced IL-6-dependent inhibition, which was abolished by LY294002, a PI3K inhibitor. Furthermore, IL-6 promoted Rho activation, and the effect was potentiated by NEU3, leading to increased cell motility that was again affected by LY294002. NEU3 silencing by siRNA resulted in the opposite: decreased Akt phosphorylation and inhibition of Rho activation. Glycolipid analysis showed a decrease in ganglioside GM3 and increase in lactosylceramide after NEU3 transfection, with these lipids apparently affecting cell apoptosis and motility. The results indicate that NEU3 activated by IL-6 exerts IL-6-mediated signaling, largely via the PI3K/Akt cascade, in a positive feedback manner and contributes to expression of a malignant phenotype in RCCs. NEU3 thus may be a useful target for RCC diagnosis and therapy.
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PMID:Plasma membrane-associated sialidase is up-regulated in renal cell carcinoma and promotes interleukin-6-induced apoptosis suppression and cell motility. 1642 83

The apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G (APOBEC3G), a member of the APOBEC family possessing DNA mutator activity through cytosine deamination, is reported to play an important role in host defense against infections such as those of hepatitis B virus and human immunodeficiency virus. Here, we examined the expression of APOBEC3G in human kidney cells to better understand its biological role against infection. APOBEC3G was immunohistochemically detectable in kidney mesangial cells and also to some extent in kidney epithelial tubular cells. In addition, overexpression of APOBEC3G was shown in renal carcinoma tissues and cell lines. APOBEC3G expression was upregulated by inflammatory cytokines, such as interferon, interleukin-6, and tumor necrosis factor. These results may provide new insight into the role of APOBEC3G in host defense against viral infection and cancer.
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PMID:Expression of APOBEC3G in kidney cells. 1721 12

Interleukin-6 (IL-6) is proinflammatory cytokine that produces multifunctional effects. It is also involved in the regulation of immune reactions, hematopoiesis and inflammatory state. Interleukin-6 has been shown to be associated with tumor progression including inhibition of cancer cells apoptosis and stimulation of angiogenesis. Anti-IL-6 therapy is a new strategy in the inflammatory autoimmune diseases and cancer. Clinical studies have shown elevated serum IL-6 concentrations in patients with endometrial cancer, non-small cell lung carcinoma, colorectal cancer, renal cell carcinoma, breast and ovarian cancer. Serum IL-6 levels correlate with tumor stage, and survival of patients. In this article we have focused on a role of IL-6 as a prognostic factor in several malignancies such as colorectal cancer, breast cancer, gastric cancer and pancreatic cancer.
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PMID:[Clinical significance of interleukin-6 (IL-6) as a prognostic factor of cancer disease]. 1803 Aug 75

Dendritic cells (DCs) are potent antigen presenting cells and represent attractive candidates for use in novel immunotherapies for patients with renal cell carcinoma (RCC), a disease that has proven refractory to conventional treatment modalities, such as chemotherapy and radiotherapy. Given the perceived need to augment antitumor type-1 immunity (TC1 and Th1) as a therapeutic end point, and the known functional plasticity of DC populations that may display heterogeneous capacity to promote T-cell responses, we sought to identify a preferred DC preparation with this capacity. We compared 2 different preparations of monocyte-derived DC using interferon-alpha (IFN-alpha) (IFN-DC and alphaDC1) with classic DCs "matured" (mDCs) using interleukin-1beta/interleukin-6/tumor necrosis factor-alpha/prostaglandin E2, for their ability to promote autologous TC1 antitumor responses from RCC patients in vitro. IFN-alpha-conditioned DC promoted significantly higher numbers of RCC-specific CD8+ T cells exhibiting a cytotoxic phenotype after in vitro stimulation (IVS) than cytokine cocktail-mDCs. Furthermore, IVS using IFN-DCs was able to diminish regulatory-type T cells among CD4+ T-cell responder populations versus IVS using conventional mDC-based vaccines. These data emphasize an important role for IFN-alpha in modulating the immunologic functions of DCs toward a polarized DC1-type capable of coordinately promoting TH1-type and TC1-type T-cell mediated immunity and supports the translational development of patient-derived IFN-alpha-conditioned DC for use in novel immunotherapies for patients with RCC, and in whom, endogenous tumor-specific TC1 effector cells may be dysfunctional, anergic, or prone to undergo apoptosis.
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PMID:Interferon-alpha (IFN-alpha)-conditioned DC preferentially stimulate type-1 and limit Treg-type in vitro T-cell responses from RCC patients. 1831 62

The immunogenic properties of renal cell carcinoma (RCC) on bone osteolysis were investigated. mRNA expression of three proinflammatory cytokines, monocyte chemotactic protein-1 (MCP-1), interleukin-6 (IL-6) and interleukin-8 (IL-8), were determined in a panel of RCC lines (CRBM 1990, ACHN and Caki-1). Moreover proinflammatory cytokine mRNA expression and protein levels of adhesion molecules, intercellular adhesion molecule-1 (ICAM-1) and E-selectin, on human umbilical vein endothelial cells (HUVEC) incubated with the conditioned media from RCC lines were evaluated. RCC express mRNA of MCP-1, IL-6 and IL-8 that may induce a proinflammatory phenotype in endothelial cells. mRNA expression of IL-6, and IL-8 was induced on HUVEC treated with the conditioned media from RCC lines and mRNA and protein levels of ICAM-1 and E-selectin were also increased. This study demonstrates the immunogenic properties of renal cell carcinoma, such as pro-inflammatory cytokine secretion and the induction of adhesion molecules (ICAM-1 and E-Sel) by endothelial cells. ICAM-1 binds lymphocyte function-associated antigen-1 (LFA-1), which is expressed by pre-osteoclasts, so that, the observed proinflammatory phenotype in HUVEC may also favour osteoclast recruitment in bone metastases microenvironment. Osteolysis in bone metastases, mediated by this pathway, may be further potentiated by the pro-angiogenic properties of RCC.
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PMID:Immunogenic properties of renal cell carcinoma and the pathogenesis of osteolytic bone metastases. 1936 Mar 51

Renal cell carcinomas (RCC) are a heterogeneous group of cancers that often include angiogenesis as a key clinical and pathological hallmark. As the transcription factor nuclear factor kappa B (NF-kappaB) has been identified as a key promoter of angiogenesis, NF-kappaB inhibitors could serve as potential anti-angiogenic agents. In this study, we tested the anti-angiogenic properties of pyrrolidine dithiocarbamate (PDTC), a NF-kappaB inhibitor, using established in vitro and ex vivo assays in human umbilical vein endothelial cells (HUVEC) and human metastatic RCC cell lines (ACHN and SN12K1). In vitro, PDTC inhibited proliferation, capillary tube formation, invasion and trans-differentiation of HUVEC. Ex vivo, PDTC blocked vessel sprouting from aortic explants and disrupted the integrity of pre-formed vessels. PDTC also inhibited the adhesion of HUVEC and RCC cells to substratum and inhibited their invasion. PDTC inhibited RCC-induced proliferation of HUVEC. Protein microarray demonstrated heterogenic actions in each cell line: in HUVEC, epidermal growth factor was significantly decreased; in ACHN, basic fibroblast growth factor, growth related oncogene, interleukin-6, RANTES and monocyte chemoattractant protein-1 (MCP-1) were significantly decreased; and in SN12K1, MCP-1 was upregulated. PDTC increased the expression of the pro-angiogenic protein interleukin-8 in both RCC cell lines. Expression of vascular endothelial growth factor (VEGF) was not significantly altered, and exogenous VEGF had a neutral effect on in vitro angiogenesis of HUVEC. Collectively, these data suggest that PDTC has some anti-angiogenic properties, which may limit development and progression of RCC.
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PMID:Anti-angiogenic actions of pyrrolidine dithiocarbamate, a nuclear factor kappa B inhibitor. 1988 12

Interleukin-6 (IL-6) is a multifunctional cytokine which plays an important role in a wide range of biologic activities in different types of cell including tumor cells. IL-6 is involved in the host immune defense mechanism as well as the modulation of growth and differentiation in various malignancies. These effects are mediated by several signaling pathways, in particular the signal transducer and transcription activator 3 (Stat3). There exists abundant evidence demonstrating that deregulated overexpression of IL-6 was associated with tumor progression through inhibition of cancer cell apoptosis, stimulation of angiogenesis, and drug resistance. Clinical studies have revealed that increased serum IL-6 concentrations in patients are associated with advanced tumor stages of various cancers (e.g., multiple myeloma, non-small cell lung carcinoma, colorectal cancer, renal cell carcinoma, prostate cancer, breast cancer and ovarian cancer) and short survival in patients. Therefore, blocking IL-6 signaling is a potential therapeutic strategy for cancer (i.e., anti-IL-6 therapy) characterized by pathological IL-6 overproduction. Preliminary clinical evidence has shown that antibody targeted IL-6 therapy was well tolerated in cancer patients. In this review, we detail the progress of the current understanding of IL-6 signaling pathway in cancer as well as an antibody targeted IL-6 therapy for human cancer.
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PMID:Interleukin-6 signaling pathway in targeted therapy for cancer. 2265 3

Renal cell carcinoma (RCC) is a highly vascular tumor associated with expression of various angiogenic growth factors. The precise process of how these growth factors are regulated in RCC is not fully understood. Recent evidence suggests that protease activated receptors (PARs), a new family of G-protein coupled receptors, play a crucial role in vascular development and tumor progression through a variety of mechanisms. However, the nature of PAR expression in human RCC tissues and its function in regulating angiogenesis in RCC are largely unknown. In this study, we investigated the expression and function of PAR-2 in RCC. RT-PCR and immunohistochemistry assays show that PAR-2 expression is significantly increased in human RCC tissue compared with the adjacent non-neoplastic kidney tissue. In RCC derived cells, PAR-2 is functional as evidenced by robust signaling through MAP kinases including ERK1/2 and JNK. Furthermore, activation of PAR-2 significantly upregulates several angiogenic cytokines, including interleukin-6 (IL-6), IL-8, monocytes chemotactic protein-1 (MCP-1) and growth-related oncogene (GRO). To our knowledge, this is the first report that characterized PAR-2 expression in RCC tissue and further demonstrated that PAR-2 has a critical role in regulating angiogenesis in RCC.
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PMID:Protease-activated receptor 2 signaling upregulates angiogenic growth factors in renal cell carcinoma. 2296 Feb 71

Renal cell carcinoma (RCC) accounts for majority of malignancies arising out of the kidney. Paraneoplastic rheumatologic manifestations; myositis, vasculitis, and arthritis have been described in a few cases with RCC. Systemic onset juvenile idiopathic arthritis (JIA) is characterized by intermittent fever, arthritis, reticulo-endothelial cell hyperplasia and absence of rheumatoid factor and antinuclear antibodies. Herein, we report a 16-year-old boy with systemic onset JIA for 5 years who developed RCC and his systemic and articular symptoms paralleled the course of RCC. The common pathophysiologic influence of the cytokine Interleukin-6 possibly played a role in the exacerbation of symptoms of systemic onset JIA during the relapse of the RCC. The case is presented to highlight the rare co-occurrence of these two diseases and their influence on each other.
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PMID:Renal cell carcinoma and systemic onset juvenile idiopathic arthritis. 2325 Feb 91


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