UNIPROT:P05231 - FACTA Search

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

This study found that the HIV-1 protease inhibitor nelfinavir (NFV) induced growth arrest and apoptosis of human prostate cancer cells (LNCaP, DU145 and PC-3 cells), as measured by MTT and terminal deoxyribonucleotide transferase-mediated dUTP nick end labeling (TUNEL) assays, respectively, on the third day of culture. In addition, NFV blocked androgen receptor (AR) signaling in association with downregulation of nuclear levels of AR in LNCaP cells as measured by reporter assay and western blot analysis. As expected, NFV downregulated the level of the AR target molecule prostate specific antigen in these cells. Moreover, NFV disrupted STAT3 signaling; protease inhibitors blocked interleukin-6-induced phosphorylation of STAT3 and inhibited STAT3 DNA binding activity in LNCaP and DU145 cells, as measured by western blot analysis and enzyme-linked immunosorbent assay (ELISA), respectively. Furthermore, NFV blocked AKT signaling in prostate cancer cells as measured by kinase assay with glycogen synthase kinase-3alpha/beta as a substrate. Importantly, NFV inhibited the proliferation of LNCaP cells presented as tumor xenografts in BALB/c nude mice without side-effects. Taken together, NFV inhibited the proliferation of prostate cancer cells in conjunction with blockade of signaling by AR, STAT3, and AKT, suggesting that this family of compounds might be useful for the treatment of individuals with prostate cancer.
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PMID:HIV-1 protease inhibitor induces growth arrest and apoptosis of human prostate cancer LNCaP cells in vitro and in vivo in conjunction with blockade of androgen receptor STAT3 and AKT signaling. 1605 14

Reciprocal interactions between tumor cells and endothelial cells constitute the most important stage of tumor metastasis. There is growing evidence suggesting that beta-estradiol and vitamin D modulate the progression of steroid-sensitive breast cancers. In keeping with those results, the purpose of the study reported here was to determine the cytotoxic and antiproliferative activity of tamoxifen (TAM) in the T47D human breast cancer cell line depending on the cell culture model (three-dimensional (3D, spheroid) or two-dimensional (2D, monolayer)) and to estimate the antiproliferative activity of vitamin D in balanced TAM/beta-estradiol conditions. The study was also designed to investigate whether vitamin D might influence interleukin-6 (IL-6) and metalloproteinase-2 (MMP-2) production in a co-culture of T47D cell spheroids with an endothelial cell monolayer in the presence of beta-estradiol and TAM. Spectrophotometric analysis with MTT revealed that the cytotoxic and antiproliferative activity of TAM was dependent on the culture model, the density of cell culture, and culture medium supplements. In balanced TAM/beta-estradiol medium, vitamin D only slightly inhibited T47D cell proliferation in both 2D and 3D cultures. Direct contact of tumor cell spheroids with the endothelium induced production of MMP-2 and IL-6, which was significantly inhibited in TAM/beta-estradiol balanced medium. Addition of vitamin D further inhibited MMP-2 production, but enhanced the production of IL-6 as was shown by ELISA assay. Our co-culture model in TAM/beta-estradiol balanced medium proved to be useful for examining direct and paracrine interactions of tumor cells with the endothelium in conditions that were closer to in vivo conditions than in the standard 2D model.
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PMID:Vitamin D, tamoxifen and beta-estradiol modulate breast cancer cell growth and interleukin-6 and metalloproteinase-2 production in three-dimensional co-cultures of tumor cell spheroids with endothelium. 1632 60

Resveratrol has been proposed to act as a chemopreventive agent in numerous epidemiologic studies and has been shown to inhibit proliferation of various tumor cells in vitro. In the present study, we investigated the antitumor effects of resveratrol on multiple myeloma (MM) cells and the mechanisms involved. Our findings indicated that resveratrol inhibited proliferation of tumor cells in a dose- [corrected] dependent manner by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and [3H]thymidine incorporation assay. Resveratrol also enhanced the inhibitory effect of dexamethasone on the growth of MM cells by MTT assay. Flow cytometric analysis demonstrated that resveratrol arrested the cells at the G1 and S phases of the cell cycle. Because nuclear factor-kappaB (NF-kappaB) plays a key role in cell survival and proliferation of human MM cells, we tested the effect of resveratrol on NF-kappaB expression by Western blot analysis and immunofluorescence. NF-kappaB was constitutively active in all human MM cell lines examined, and resveratrol down-regulated NF-kappaB expression in all cell lines. Resveratrol also down-regulated the expression of NF-kappaB-regulated gene products by Western blot analysis, gelatin zymography, and enzyme-linked immunosorbent assay, including interleukin-6, Bcl-2, Bcl-xL, XIAP, c-IAP, vascular endothelial growth factor (VEGF), and matrix metalloproteinase-9 (MMP-9), which modulates an array of signals controlling cellular survival and proliferation and tumor promotion. Indeed, annexin V-fluoroisothyocyanate and Transwell invasion analyses revealed that incubation of MM cells with resveratrol resulted in apoptotic cell death and inhibition of invasion. In conclusion, these data suggest that resveratrol is an effective in vitro inhibitor of NF-kappaB in human MM cells. Resveratrol plays a role in suppressing the proliferation of MM cells and induces apoptosis, thus providing the molecular basis for the treatment of MM patients with this compound.
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PMID:Resveratrol downregulates the constitutional activation of nuclear factor-kappaB in multiple myeloma cells, leading to suppression of proliferation and invasion, arrest of cell cycle, and induction of apoptosis. 1649 May 92

To explore the effect of arsenic trioxide (As2O3) on growth and secretion of interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) of bone marrow stroma cells (BMSC) from the patients with multiple myeloma (MM). Specimens of bone marrow aspiration from MM patients were used to establish BMSC cultures. BMSC and human MM cell line CZ-1 were cultured together or alone in the absence or presence of As2O3 at various concentrations (1-20.0 micromol/L). Cell growth inhibition was assessed by MTT assay, cytokines in the culture supernatants were measured with ELISA. The results showed that As2O3 had cytostatic effect on CZ-1 with fifty percent growth inhibition (IC50) for 48 hours at 2.3 micromol/L. As2O3 did not inhibit the growth of BMSC. High levels of IL-6 and VEGF have been found in the culture supernatants of BMSC from MM patients. Cytokine production of BMSC treated with As2O3 significantly decreased as compared with controls (P < 0.05). Excitingly, even the increased cytokine production triggered by adhesion of MM cell and BMSC was also inhibited by As2O3. It is concluded that As2O3 has no inhibitory effect on cell growth of BMSC, but inhibit the production of IL-6 and VEGF by BMSC.
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PMID:[Effect of arsenic trioxide on bone marrow stromal cells of patients with multiple myeloma]. 1663 92

Cancer cells may often support their own growth, survival, and drug resistance by autocrine/paracrine loops based on the production of different factors; results from us and others have shown that similar interleukin-6 (IL-6)-related loops are operative in multiple myeloma and prostate or renal cancer. Because this aspect has not been investigated in detail for hepatocellular carcinoma (HCC), we have examined it in HA22T/VGH cells. These differ from other primary liver cancer cell lines (that is, HepG2, HuH-6, and HuH-7) in that enzyme-linked immunosorbent assay (ELISA) showed the HA22T/VGH cells to secrete remarkable amounts of IL-6 (16.8 ng/10(6) cells/24 h); this production, due to constitutive activation of NF-kappaB, is inhibited by agents like curcumin and dehydroxymethylepoxyquinomicin (DHMEQ), which interfere with the transcription factor. Flow cytometry, ELISA, mRNA, and Western blotting analyses were performed to characterize the status of the IL-6 receptor in HA22T/VGH cells. Two transmembrane glycoproteins that form the functional IL-6 receptor have been identified: the ligand-binding gp80 and the signal-transducer gp130. Soluble forms of gp80 also trigger membrane gp130 signaling when complexed with IL-6, while soluble forms of gp130 inhibit the same process. Our results showed that HA22T/VGH cells express gp130 at their surface, but release only traces of its soluble form. For gp80, the cells produced the mRNAs of both its membrane and soluble form. However, in immunoblotting they exhibited a very faint content of the same subunit, which, in addition, was neither expressed at the cell surface nor secreted. In MTT assays, incubation with a neutralizing anti-IL-6 antibody for up to 7 days did not affect the growth of HA22T/VGH cells. Also, other specific anti-IL-6 approaches (siRNA or AODN) failed to produce this result. In conclusion, autostimulatory loops mediated by IL-6 are less likely to occur in HCC than in other kinds of cancer. However, since release of IL-6 is frequent in HCC, especially in its more advanced stages, the use of agents like curcumin or DHMEQ might be beneficial to counteract its adverse systemic effects (e.g., cachexia).
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PMID:Significance of autologous interleukin-6 production in the HA22T/VGH cell model of hepatocellular carcinoma. 1726 74

Previous studies have reported little correlation between the relative toxicity of particle types when comparing lung toxicity rankings following in vivo instillation versus in vitro cell culture exposures. This study was designed to assess the capacity of in vitro screening studies to predict in vivo pulmonary toxicity of several fine or nanoscale particle types in rats. In the in vivo component of the study, rats were exposed by intratracheal instillation to 1 or 5 mg/kg of the following particle types: (1) carbonyl iron (CI), (2) crystalline silica (CS) (Min-U-Sil 5, alpha-quartz), (3) precipitated amorphous silica (AS), (4) nano-sized zinc oxide (NZO), or (5) fine-sized zinc oxide (FZO). Depending on particle type and solution state, these particles range in size from 90 to 500 nm in size. Following exposures, the lungs of exposed rats were lavaged and inflammation (neutrophil recruitment) and cytotoxicity end points (bronchoalveolar lavage [BAL] fluid lactate dehydrogenase [LDH] values) were measured at 24 h, 1 week, 1 and 3 months postexposure. For the in vitro component of the study, three different culture conditions were utilized. Cultures of (1) rat L2 lung epithelial cells, (2) primary alveolar macrophages (AMs) (collected via BAL from unexposed rats), as well as (3) AM-L2 lung epithelial cell cocultures were incubated with the particle types listed above, and the culture fluids were evaluated for cytotoxicity end points (LDH, 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan [MTT]) as well as inflammatory cytokines (macrophage inflammatory 2 protein [MIP-2], tumor necrosis factor alpha [TNF-alpha], and interleukin-6 [IL-6]) at one (i.e., cytokines) or several (cytotoxicity) time periods. Results of in vivo pulmonary toxicity studies demonstrated that instilled CI particles produced little toxicity. CS particles produced sustained inflammation and cytotoxicity. AS particles produced reversible and transient inflammatory responses. NZO or FZO particles produced potent but reversible inflammation which was resolved by 1 month postinstillation exposure. Results of in vitro pulmonary cytotoxicity studies demonstrated a variety of responses to the different particle types, primarily at high doses. With respect to the LDH results, L2 cells were the most sensitive and exposures to nano- or fine-sized ZnO for 4 or 24 h were more cytotoxic than exposures to CS or AS particles. Macrophages essentially were resistant and epithelial macrophage cocultures generally reflected the epithelial results at 4 and 24 h incubation, but not at 48 h incubation. MTT results were also interesting but, except for nano- and fine-sized ZnO, did not correlate well with LDH results. Results of in vitro pulmonary inflammation studies demonstrated that L2 cells did not produce MIP-2 cytokines, but CS- or AS-exposed AMs and, to a lesser degree, cocultures secreted these chemotactic factors into the culture media. Measurements of TNF-alpha in the culture media by particle-exposed cells demonstrated little activity. In addition, IL-6 secretion was measured in CS, AS, and nano-sized ZnO-exposed cocultures. When considering the range of toxicity end points to five different particle types, the comparisons of in vivo and in vitro measurements demonstrated little correlation, particularly when considering many of the variables assessed in this study-such as cell types to be utilized, culture conditions and time course of exposure, as well as measured end points. It seems clear that in vitro cellular systems will need to be further developed, standardized, and validated (relative to in vivo effects) in order to provide useful screening data on the relative toxicity of inhaled particle types.
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PMID:Assessing toxicity of fine and nanoparticles: comparing in vitro measurements to in vivo pulmonary toxicity profiles. 1730 Oct 66

Microporous scaffolds with potential applications for tissue engineering were produced from the biodegradable aliphatic isosorbide-based polyurethane using a combined salt leaching-solvent evaporation-coagulation process. Alkaline sodium phosphate heptahydrate crystals were used as a solid porogene, and acetone-water mixture was used as a nonsolvent-coagulant. The scaffolds used in this study had interconnected pores with sizes in the range of 70-120 microm and a pore-to-volume ratio of 87%. The XPS measurements showed that the residence of the scaffold in an aqueous solution of the alkaline porogene changed its surface atomic composition, that is increased the surface concentration of oxygen and nitrogen and reduced the surface concentration of hydrocarbons relative to the control material. This also enhanced the hydrophilicity of the scaffold's surfaces as assessed from contact angle measurements. The alkaline porogene did not affect the polymer's molecular weight. The MTT cytotoxicity assay showed that the isosorbide-based polyurethane scaffold is noncytotoxic. The amounts of interleukin-6 and interleukin-8 proinflammatory cytokines released from human blood leukocytes exposed to the polyurethane scaffolds in vitro were comparable and/or lower than the amount of the cytokines released by leukocytes exposed to the culture-grade polystyrene control.
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PMID:Structure-property relations and cytotoxicity of isosorbide-based biodegradable polyurethane scaffolds for tissue repair and regeneration. 1772 56

The study is to investigate the effect of asiaticoside on collagen-induced arthritis (CIA). The model of CIA mice was prepared and the change of secondary paw swelling and the arthritis scores were observed. In vitro proliferation of spleen cells was examined using MTT assay. The cell-free protein extracts from the arthritic joints and nonarthritic joints were used for the analysis of protein expression of cyclooxygenase-2 (COX-2). And the level of PGE2 in joints was assayed using PGE2 express EIA kit. The tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels in the serum were measured by ELISA. Histopathological examination was performed by hematoxylin-eosin (HE) stain method. Asiaticoside (10, 20 and 40 mg x kg(-1) x d(-1), 22 d, ig) significantly reduced paw swelling, and decreased the arthritis scores. There was a significant reduction in proliferation of spleen cells of CIA mice treated with asiaticoside as compared with that of untreated CIA mice. COX-2, PGE2, TNF-alpha and IL-6 production in CIA mice were inhibited by asiaticoside. Meanwhile, the pathological examination showed that articular cartilage degeneration with synovial hyperplasia and inflammatory cells infiltration in CIA mice was suppressed by asiaticoside. Its active mechanism may be related to inhibiting proliferation of lymphocyte and reduction of expression of COX-2 and inflammatory cytokines.
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PMID:[Inhibitiory action of asiaiticoside on collagen-induced arthritis in mice]. 1788 51

In this study, we investigated the potential of an elastic salmon collagen gel (e-gel) for use as stretching culture scaffold. First, human umbilical vein endothelial cells (HUVECs) were cultured on the e-gel under static condition, and their growth was evaluated by DNA content measurement, MTT test, and scanning electron microscopy. The results demonstrated steady increases in cell number with culture time. Next, HUVECs were cultured on the e-gel under static condition for 2 d, then uniaxially stretched at a constant frequency (10% elongation at 1 Hz). After the stretching culture for 2 h, the cells oriented perpendicularly to the stretch direction. Moreover, the interleukin-6 and interleukin-8 productions of the cells significantly increased under the stretch condition compared with those under the static condition. These results were in good agreement with the published data in which an elastic silicone membrane was used as a scaffold. In conclusion, the e-gel can be used for stretching culture for vascular tissue engineering.
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PMID:Application of elastic salmon collagen gel to uniaxial stretching culture of human umbilical vein endothelial cells. 1855 48

Electricity has a long history of being used as an alternative clinical treatment and as an effective approach to modifying cellular behaviours in vitro. It has been difficult, however, to take advantage of this modality in tissue generation because of the lack of suitable conductive, biocompatible scaffolding materials. In this study, in order to electrically regulate cell activities, a largely biodegradable conductor made of 5% conductive polypyrrole and 95% biodegradable poly(L-lactide) (PPy/PLLA) was prepared. Human cutaneous fibroblasts were cultured on the conductors in the presence or absence of a direct current (DC) electrical field (EF) of 50 mV/mm. The growth of the cells was characterized using fluorescent staining, SEM, and a MTT assay. The RNA expressions of interleukin-6 (IL-6) and interleukin-8 (IL-8) were assayed by RT-PCR. The amounts of IL-6 and IL-8 secreted by the fibroblasts were quantified by ELISA. The results showed that the PPy/PLLA conductors supported cell adhesion, spreading, and proliferation in both the presence and absence of the EF. Electrical stimulation (ES) applied through PPy/PLLA conductors dramatically enhanced cytokine secretion approximately 10-fold when compared to the non-ES controls. This effect lasted several days after the end of the ES. These findings highlight for the first time the possibility of a potent, effective approach to regulating tissue regeneration in conductive scaffolds through ES-modulated cytokine secretion, and to increasing cytokine productivity for biotechnological applications.
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PMID:The regulation of cell functions electrically using biodegradable polypyrrole-polylactide conductors. 1860 89

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