UNIPROT:P05231 - FACTA Search

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)

In an attempt to provide information useful for improving tumor immunotherapy, we examined the lymphokine requirements for generation of cytotoxic T lymphocytes (CTL) from C57BL/6 murine thymocytes. Our previous work indicated that interleukin-6 (IL-6) is involved in the maturation of CTL in vitro. Using a standard chromium 51 release assay and P815 mastocytoma tumor cells as targets, we found that after 66 hours of in vitro culture, a much greater CTL response was generated in the presence of interleukin-2 (IL-2) plus IL-6 (70.5% +/- 10.6%) compared with that generated in the presence of IL-2 only (25.2% +/- 1.0%). After 72 hours of culture, however, this difference was no longer significant, with cultures incubated with both IL-2 and IL-6 yielding 70.6% +/- 1.8% lysis versus 64.5% +/- 3.4% for cultures incubated with IL-2 only. To attempt to understand this difference, we examined the production of IL-6 in thymocyte cultures using a cell line, PC-6, that proliferates in the presence of IL-6. We found that the CTL response generated from unfractionated murine thymocytes in the presence of concanavalin A plus IL-2 correlated with production of IL-6 by cells within the thymic population. These data suggest that the generation of a CTL response in the absence of added IL-6 is due to the production of this ubiquitous lymphokine by thymocytes on in vitro culture. We present this as further evidence that IL-6 is necessary for the development of functional CTL from murine thymocytes and may therefore play a role in the development of effective tumor immunotherapy.
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PMID:Production of interleukin-6 in vitro parallels development of cytotoxic T lymphocytes from murine thymocytes. 278 17

We investigated the relationship between the toxic effects of metal wear particles and their ability to stimulate the release of inflammatory mediators implicated in bone resorption. In vitro studies were carried out with use of rat peritoneal macrophages, which were exposed to either cobalt-chromium-alloy or titanium-aluminum-vanadium particles, milled from the metal components of hip prostheses. The particles were in the size-range of, and at concentrations similar to, those found in the tissues surrounding failed prostheses in humans. The titanium-aluminum-vanadium particles showed little toxicity even at high concentrations, while the cobalt-chromium particles were very toxic. The titanium-aluminum-vanadium particles induced significantly more release of prostaglandin E2 than did the cobalt-chromium particles, and this was true for a wide range of concentrations. Exposure to titanium-aluminum-vanadium increased the release of prostaglandin E2, interleukin-1, tumor necrosis factor, and interleukin-6. In contrast, exposure to cobalt-chromium particles was associated with a decreased release of prostaglandin E2 and interleukin-6, and it had little effect on the release of interleukin-1 and tumor necrosis factor.
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PMID:The differences in toxicity and release of bone-resorbing mediators induced by titanium and cobalt-chromium-alloy wear particles. 831 20

The release of metals from total joint prostheses may contribute to periprosthetic bone loss manifested as osteolysis. The effects of titanium, cobalt, and chromium on human osteogenic sarcoma cells (osteoblastlike cells) were investigated in vitro. Titanium, cobalt, and chromium at concentrations of 1, 10, and 100 ng/ml did not cause any changes in the cell growth, viability, and injury after 72-hour incubation with the cells. Titanium, cobalt, and chromium at concentrations ranging from 0.01 to 100 ng/ml significantly enhanced the release of interleukin-1 beta and tumor necrosis factor-alpha by lipopolysaccharide stimulated human osteogenic sarcoma cells, whereas they did not alter the release of transforming growth factor-beta 1. Cobalt at concentrations ranging from 0.1 to 100 ng/ml significantly enhanced the release of interleukin-6, but titanium and chromium did not. Cobalt and chromium at concentrations of 10 and 100 ng/ml significantly inhibited the release of osteocalcin by human osteogenic sarcoma cells, whereas titanium had no effect. Titanium, cobalt, and chromium at concentrations of 10 and 100 ng/ml significantly inhibited the synthesis of Type I collagen by human osteogenic sarcoma cells. Cobalt and chromium inhibited the cell proliferation in response to lipopolysaccharide stimulation, whereas titanium did not. The data presented in this article suggest that the metal induced disregulation of cytokine release and osteoblast dysfunction may play an important role in the induction of osteolysis in patients with total joint arthroplasties.
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PMID:Prosthetic metals interfere with the functions of human osteoblast cells in vitro. 918 23

Cytokines and proteases are secreted by fibroblasts in response to particulate wear debris, and these proteins are felt to play an important role in the development of osteolysis and implant loosening. Although metallic and polyethlyene debris have been studied extensively, little is known about the cellular responses to hydroxyapatite, despite the wide clinical use of these materials. Therefore, the effects of hydroxyapatite (HA) and hydroxyapatite/beta-tricalciumphosphate (HA/TCP) on cellular proliferation, cytokine gene expression and protein secretion, protease synthesis, and gelatinolytic activity were investigated in human fibroblasts. HA and HA/TCP particles were synthesized, and their effects were compared to the responses elicited by titanium and cobalt chromium. Sample characterization by scanning electron microscopy and Coulter Counter demonstrated that the materials had a mean particle size of less than 10 microm, and all of the particles were compared using the same concentration ranges. Aliquots of particle suspensions were added to human fibroblasts maintained in tissue culture, and dose-response and time-course experiments were performed. Effects of the particles on fibroblast proliferation were assessed, and alterations in cytokine levels were determined by specific enzyme linked immunosorbent assays (ELISA). Cytokines that were evaluated included interleukin-1 (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha), all of which have been demonstrated to enhance bone resorption and are associated with osteolysis and implant loosening. Gene expression was determined using Northern blot analysis with cytokine-specific probes, while secretion of the proteases collagenase and stromelysin was determined by Western blot analysis. Functional gelatinolytic assay was assessed using zymogram gels. The particles were evaluated in a concentration range from 0.000021 to 0.021 vol%. All of the particles produced increases in cellular proliferation up to 0.0021 vol%, with the largest increases being seen at 0.021 vol% with HA/TCP and titanium. At the highest concentration, both cobalt chromium and HA samples decreased cellular proliferation relative to lower doses, possibly representing cytotoxicity. Hydroxyapatite particles yielded a 30-fold increase in interleukin-6 secretion compared to unstimulated controls, which was also greater than three times the levels produced by cobalt chromium, titanium, or HA/TCP. HA particles also tripled the secretion of IL-1beta at 0.00021 vol%, and doubled TNF-alpha secretion at 0.021 vol%. Addition of conditioned media prepared by incubation of the particles in culture medium in the absence of cells did not alter the secretion of any of the cytokines. Northern blot analysis using IL-6 probes also demonstrated strong increases with HA compared to the other materials, suggesting that the action of the HA particles was at the level of transcription. Secretion of the protease collagenase was increased by all of the samples including HA when compared to unstimulated controls. Stromelysin secretion into the culture medium was decreased by cobalt chromium, but increased by titanium, HA, and HA/TCP. All of the particles including HA increased the gelatinolytic activity of the fibroblasts. These findings demonstrate that HA and HA/TCP particles are capable of stimulating the expression and secretion of cytokines and proteases that enhance bone resorption, and suggest that particulate debris from implants using these coatings may also increase osteolysis and loosening.
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PMID:Effects of hydroxyapatite particulate debris on the production of cytokines and proteases in human fibroblasts. 1151 71

Regarding orthopaedic implant loosening it has been hypothesized that particle-activated macrophages release interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha). This in turn stimulates osteoblasts to release interleukin-6 (IL-6) and prostaglandin E(2) (PGE(2)). These mediators recruit and activate osteoclasts and may therefore lead to bone resorption and loss of implant fixation. In this study we compared the ability of different materials to induce the release of IL-6 and PGE(2) from primary isolated, human osteoblasts without preceding activation by macrophages. We tested stainless steel, cobalt-chromium alloy (CoCrMo), commercially pure titanium (cpTi), Ti-6Al-7Nb and Ti-6Al-4V processed in the same manner as corresponding clinical implants. After 12 and 24h the cells had actively secreted IL-6 and PGE(2). There were no clear differences among the implant materials or with the plastic control. The amount of factors the cells released in our study compare well with the findings of other authors who investigated osteoblasts on plastic. In comparison with the literature these amounts are lower than secretion levels of osteoblasts stimulated with implant particles, IL-1 or TNF-alpha. Moreover, other authors found that osteoclasts require higher concentrations of PGE(2) to become activated than the concentrations measured in our experiments. Therefore, the amount of PGE(2) released from the osteoblasts in our study is probably not sufficient to induce osteolytic activity. Because of contradictory statements in the literature it is unclear if the measured IL-6 concentrations promote osteolytic activity. Differences in material composition does not significantly influence the release of these factors if the materials have similar surface roughnesses.
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PMID:IL-6 and PGE2 release by human osteoblasts on implant materials. 1285 49

More than half of the U.S. population has a body mass index of 25 kg/m2 or more, which classifies them as overweight or obese. Obesity is often associated with comorbidities such as diabetes, cardiovascular diseases, and cancer. CLA and chromium have emerged as major dietary supplements that reduce body weight and fat mass, and increase basal metabolic rate in animal models. However, studies show that CLA induces insulin resistance in mice and in humans, whereas Cr improves insulin sensitivity. Hence, we designed the present study to examine the combined effect of CLA and Cr on body composition and insulin sensitivity in a Balb/c mice (n = 10/group) model of high-fat-diet-induced obesity. CLA alone lowered body weight, total body fat mass, and visceral fat mass, the last of which decreased further with the combination of CLA and Cr. This effect was accompanied by decreased serum leptin levels in CLA-fed and CLA + Cr-fed mice, and by higher energy expenditure (EE) and oxygen consumption (OC) in CLA + Cr-fed mice. Serum levels of glucose, insulin, the pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6), as well as insulin resistance index (IRI), decreased with CLA, whereas CLA and Cr in combination had significant effects on insulin and IL-6 concentrations and IRI. In summary, CLA + Cr decreased body weight and fat mass in high-fat-diet-fed mice, which may be associated with decreased leptin levels and higher EE and OC.
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PMID:Conjugated linoleic acid and chromium lower body weight and visceral fat mass in high-fat-diet-fed mice. 1693 88

Elevated blood levels of the proinflammatory cytokines interleukin-6 (IL-6), interleukin-8 (IL-8), and MCP-1 (monocyte chemoattractant protein-1) increase insulin resistance and the risk of cardiovascular disease (CVD). There is no previous study that has examined the effect of ketosis and trivalent chromium on IL-6, IL-8, or MCP-1 secretion in any cell type or in human or animal model. The authors examined the hypothesis that ketosis increases and trivalent chromium decreases the levels of cytokines and oxidative stress in diabetes using a U937 monocyte cell culture model. Cells were cultured with control, high glucose (HG), and acetoacetate (AA) in the absence or presence (0.5-10 microM) of CrCl(3), chromium picolinate (Cr-P), or chromium niacinate (Cr-N) at 37 degrees C for 24 h. The data show a significant stimulation of IL-6, IL-8, and MCP-1 secretion and an increase in oxidative stress in cells treated with HG or AA. The effect of HG on cytokine secretion was reduced by Cr-N, and to a lesser extent by CrCl(3) and Cr-P. The effect of HG on oxidative stress was reduced by Cr-N and CrCl 3, but not by Cr-P. Similarly, Cr-N decreased the cytokine secretion in HG + AA-treated cells. Cr-N significantly decreased standard oxidant (H(2)O(2)) induced cytokine secretion, which suggests that reduction of cytokine secretion by Cr-N is in part mediated by its antioxidative effect. In a cell culture model, Cr-N appears to be the most effective form of chromium in inhibiting oxidative stress and proinflammatory cytokine secretion by monocytes. This study suggests that chromium niacinate supplementation may be useful in reducing vascular inflammation and the risk of CVD in diabetes.
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PMID:High glucose and ketosis (acetoacetate) increases, and chromium niacinate decreases, IL-6, IL-8, and MCP-1 secretion and oxidative stress in U937 monocytes. 1766 66

Wear debris-induced osteolysis is purportedly the limiting problem affecting the long term results of joint arthroplasty. Pathogenic effects of wear debris in peri-implant cells such as macrophages, osteoblasts and osteoclasts have been well studied. In contrast, the effects of wear debris on osteocytes, which make up over 90% of all bone cells, remain unknown. We hypothesized that metal implant debris can induce the pro-inflammatory response in osteocytes. This study demonstrated the effects of cobalt-chromium-molybdenum alloy (Co-Cr-Mo) particles on a well-characterized MLO-Y4 osteocyte cell line. Co-Cr-Mo alloy particle treatment significantly (p<0.05) up-regulated tumor necrosis factor alpha (TNFalpha) gene expression after 3 and 6 h and TNFalpha protein production after 24 h, but down-regulated interleukin-6 (IL-6) gene expression after 6 h. Co-Cr-Mo alloy particle treatment also induced osteocyte apoptosis after 24 h. This apoptotic effect was partially (40%) dependent on TNFalpha. Therefore, our results suggest that osteocytes play a role in particle-induced inflammation and bone resorption following total joint arthroplasty by inducing pro-inflammatory cytokines and inducing osteocyte apoptosis.
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PMID:Co-Cr-Mo alloy particles induce tumor necrosis factor alpha production in MLO-Y4 osteocytes: a role for osteocytes in particle-induced inflammation. 1949 95

Chromated copper arsenate, which is used worldwide as a wood preservative, can adversely affect human health. Accumulating evidence suggests that chromium (Cr) and arsenic (As) can potentially disrupt the redox balance and cause respiratory diseases and cancer in humans. The present study was designed to determine the combined toxic effects of these metals in the lungs and to clarify the specific molecules that are stimulated by combined exposure to both metals. Male C57BL/6J mice were intratracheally instilled with arsenate [As(V)], hexavalent chromium [Cr(VI)], or a combination of both metals. Mice were sacrificed 2 days after treatment to collect bronchoalveolar lavage fluid and lung tissue samples. Inflammation, cytotoxicity, apoptosis, and oxidative stress markers were measured. Our results indicated that administration of Cr(VI) alone or in combination with As(V) induced neutrophil-dominant inflammation as well as phosphorylation of mitogen-activated protein kinases; effects of treatment with As(V) alone were comparatively less potent. By analyzing the production of interleukin-6 and activity of lactate dehydrogenase and caspase, we confirmed that co-treatment intensified pulmonary injury and that it was accompanied by oxidative stress, as confirmed by marked increases in the production of reactive oxygen species, reduced glutathione content, and thioredoxin reductase (TRXRD) activity. Expressed mRNA levels of heme oxygenase-1, glutamylcysteine ligase, glutathione peroxidase 2, thioredoxin (TRX) 1, and TRXRD1 were also enhanced by co-treatment, whereas treatment with As(V) alone reduced the mRNA expression level of TRX2. Our data suggest that co-treatment with As(V) exacerbated Cr(VI)-induced pulmonary injury and that this effect may be exerted through a disruption in the balance among several antioxidant genes.
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PMID:Pulmonary injury and antioxidant response in mice exposed to arsenate and hexavalent chromium and their combination. 1989 65

Astringinin can attenuate organ injury following trauma-hemorrhage, the mechanism remains unknown. Protein kinase B/hemeoxygenase-1 (Akt/HO-1) pathway exerts potent anti-inflammatory effects in various tissues. The aim of this study is to elucidate whether Akt/HO-1 plays any role in astringinin-mediated attenuation of hepatic injury following trauma-hemorrhage. For study this, male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure 35-40 mmHg for 90 min) followed by fluid resuscitation. A single dose of astringinin (0.3 mg/kg body weight) with or without a PI3K inhibitor (wortmannin) or a HO antagonist (chromium-mesoporphyrin) was administered during resuscitation. Various parameters were measured at 24 h post-resuscitation. Results showed that trauma-hemorrhage increased plasma aspartate and alanine aminotransferases (AST and ALT) concentrations and hepatic myeloperoxidase activity, cytokine induced neutrophil chemoattractant (CINC)-1, CINC-3, intercellular adhesion molecule-1, and interleukin-6 levels. These parameters were significantly improved in the astringinin-treated rats subjected to trauma-hemorrhage. Astringinin treatment also increased hepatic Akt activation and HO-1 expression as compared with vehicle-treated trauma-hemorrhaged rats. Co-administration of wortmannin or chromium-mesoporphyrin abolished the astringinin-induced beneficial effects on post-resuscitation pro-inflammatory responses and hepatic injury. These findings collectively suggest that the salutary effects of astringinin administration on attenuation of hepatic injury after trauma-hemorrhage are likely mediated via Akt dependent HO-1 up-regulation.
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PMID:Mechanism of salutary effects of astringinin on rodent hepatic injury following trauma-hemorrhage: Akt-dependent hemeoxygenase-1 signaling pathways. 2202 64

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