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

Endothelins are a class of peptides that are produced by and elicit responses in many tissues. A growing literature documents the presence and effects of endothelins in bone. Both endothelinA and endothelinB receptors have been demonstrated in osteoblastic cells by ligand binding. Major signal transduction pathways for endothelin in bone cells appear to be stimulation of phospholipid turnover, by activation of A, C and D phospholipases, stimulation of calcium flux from intracellular and extracellular stores and activation of tyrosine kinases. Endothelins also modulate calcium signaling elicited by other agents in osteoblastic cells. The parathyroid hormone-stimulated calcium transient in UMR-106 cells is enhanced by endothelins, acting through an endothelinB receptor, whereas the parathyroid hormone-stimulated increase in cyclic AMP is inhibited by endothelins. Phenotypic responses to endothelin-1 include changes in alkaline phosphatase activity, stimulation of osteocalcin and osteopontin message, stimulation of collagen and noncollagenous protein synthesis, inhibition of osteoclast motility and stimulation of prostaglandin-dependent resorption. Endothelin-1 also enhances the interleukin-1-induced increase in interleukin-6. Endothelins can also potentially affect calcium metabolism through their actions to inhibit the secretion of parathyroid hormone.
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PMID:Endothelin receptors, second messengers, and actions in bone. 760 88

This study was designed to evaluate whether the sequential monitoring of serum interleukin-6 levels (SIL-6) could be helpful for diagnosing the occurrence of hepatic allograft rejection. An SIL-6 post-transplant study was conducted on nine cynomolgus monkeys which had undergone orthotopic hepatic allotransplantation, six of which were treated with FK-506 (a new immunosuppressant agent isolated from Streptomyces tsukubaensis) and three of which were not. All the nontreated animals showed biochemical abnormalities from days 5-6, characterized by a marked elevation of serum alkaline phosphatase levels, and they eventually died on days 8, 12, and 63 (group I). Acute cellular rejection was confirmed by histological study of the hepatic grafts taken at autopsy or biopsy. On the other hand, four of the treated animals (group IIa) survived more than 30 days. Biochemical examination of this group showed no abnormal signs apart from a slight elevation of alkaline phosphatase (< 2000 IU/l). Histological examination carried out around 30 days after transplantation revealed a transient infiltration of polynuclear cells into Glisson's area, with the portal vein and bile duct remaining intact. The remaining two animals (group IIb) died of dehydration and arterial thrombosis on days 5 and 7, respectively. A kinetic study of SIL-6 conducted during the first 2 weeks showed quite different patterns among the three groups. All recipients in group I demonstrated two peaks following grafting on days 1 and 3 or 4, the second peak of above 2.0 U/ml preceding biochemical abnormalities by 2 to 3 days.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serum interleukin-6 levels as an indicator of acute rejection after liver transplantation in cynomologous monkeys. 768 73

The role of interleukin-6 in the bone microenvironment is controversial. We studied the effect of recombinant human interleukin-6 (rhIL-6) administration on bone metabolism in 10 adult female rhesus monkeys (age 12-27 years). Monkeys received rhIL-6 (15 micrograms/kg/day) daily by subcutaneous injection for 28 days. Serum alkaline phosphatase, osteocalcin, and 24 h urinary calcium excretion were determined before, during (at weeks 2 and 4), and after (at week 6) treatment. Transilial biopsies (right and left) were obtained before treatment was initiated and just after the final (28th) dose at week 4. The serum alkaline phosphatase significantly increased at 2 and 4 weeks of rhIL-6 administration. Osteocalcin and urinary calcium excretion significantly decreased at week 2. Upon treatment with rhIL-6 significant reductions in OS/BS and Ob.S/BS were observed without changes in other static histomorphometry parameters. The reductions in urinary calcium excretion, serum osteocalcin, and the static bone parameters are consistent with an IL-6 induced reduction in bone formation or turnover. Whether this pharmacologic effect is relevant at the physiologic level remains to be determined.
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PMID:Effects of recombinant human interleukin-6 administration on bone in rhesus monkeys. 799 21

Leukemia inhibitory factor (LIF) is structurally related to interleukin-6 (IL-6), oncostatin M (OSM), and ciliary neurotrophic factor (CNTF). Since LIF-deficient mice do not exhibit overt phenotypic effects in cell types known to be targets for LIF action in vitro, we examined the ability of IL-6, OSM, and CNTF to reproduce the effects of LIF in five different bioassays. OSM, CNTF, and LIF are able to promote embryonic stem cell growth and to maintain them in an undifferentiated state as marked by a high alkaline phosphatase activity (ED50 are, respectively, 0.5, 3 and 1 ng/ml). Whereas LIF and OSM maintain close to 100% of ES cells in an undifferentiated state, CNTF, at optimal concentrations, prevents differentiation of only 60% of the ES population. Murine 7TD1 hybridoma cell growth is induced only in the presence of IL-6 (ED50 = 0.1 ng/ml). Both LIF and OSM stimulate DA1a cell proliferation (ED50 are, respectively, 1 and 12 ng/ml). OSM appears, therefore, to act as a weak agonist of LIF-dependent processes on murine cells, however, with a 10-fold lower specific activity than that of LIF, which is in agreement with human OSM cross-reacting with the murine LIF-R. Though IL-6, LIF, and OSM all stimulate haptoglobin and fibrinogen production by human HepG2 hepatoma cells, the dose-response curves of these three factors exhibit very different characteristics. CNTF stimulates acute-phase protein production by HepG2 cells only at high concentrations (greater than 1 microgram/ml). A549 epithelial cells are subjected to growth inhibition only in the presence of OSM (ED50 = 6 ng/ml), even though they expressed LIF-R and gp130 transcripts. These data suggest that OSM and LIF act on human cells through different receptors. Altogether, these results indicate that none of the factors examined in this study are precisely interchangeable in terms of their biological actions.
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PMID:Are LIF and related cytokines functionally equivalent? 805 Apr 91

Conditioned media of human glial cell lines induced alkaline phosphatase activity in cultured calf artery endothelial cells. The maximal alkaline phosphatase activity in the culture was comparable to the level in isolated brain capillary endothelial cells. An induction factor in the conditioned media was purified and identified as interleukin-6 from its amino-terminal sequence, molecular weight, amino acid composition and immunoreactivity. Recombinant interleukin-6 had similar induction activity. Our findings raise the possibility that interleukin-6 induces and modulates alkaline phosphatase activity in endothelial cells during normal development of the blood-brain barrier and under certain pathological conditions.
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PMID:Conditioned media of glial cell lines induce alkaline phosphatase activity in cultured artery endothelial cells. Identification of interleukin-6 as an induction factor. 806 34

Structure-function studies of cytokines require that simple, sensitive and reliable biological assays are available. A well known property of interleukin-6 (IL-6) is that of being able to induce transcription from several liver-specific promoters in human hepatoma cells. However, the available assays of IL-6 in hepatoma cells, which are either based on the detection of increased expression of endogenous acute phase response genes or on the activation of reporter genes transfected under the control of IL-6 responsive promoters, are not very sensitive and are time consuming. We have established a new assay for IL-6 in hepatoma cells which is based on the transfection of an IL-6 inducible promoter/secreted alkaline phosphatase (SEAP) gene fusion and which measures the inducible production and release of SEAP in the culture medium. SEAP activity is measured with a simple colorimetric assay that requires no cell manipulation, thus allowing a large set of samples to be analysed simultaneously. The CRP/SEAP assay can be used in studies on the structure-function relationships of human IL-6.
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PMID:A fast and sensitive colorimetric assay for IL-6 in hepatoma cells based on the production of a secreted form of alkaline phosphatase (SEAP). 815 87

Using in situ hybridization, we investigated the expression of mRNA for interleukin-1 beta (IL1 beta), interleukin-6 (IL6), and transforming growth factor-beta-1 (TGF beta 1) in sections of developing bone in human osteophytes. The expression was related to the cellular activity of alkaline phosphatase to aid in the identification of pre-osteoblast populations. IL1 beta mRNA was localized in active osteoblasts within distinct areas of intramembranous ossification. However, the expression was sporadic and appeared to occur at a specific stage of the osteoblast life cycle. There was no IL1 beta mRNA expression in any cell types during endochondral ossification. IL6 mRNA expression was located within pre-osteoblasts and in newly differentiated and matrix-secreting osteoblasts; expression was absent or reduced in flattened, inactive osteoblasts. Weak or no IL6 expression was observed in chondroblasts and chondrocytes, respectively. However, there was a close association between IL6 mRNA expression and the differentiation of mesenchymal cells into osteoblasts. TGF beta 1 expression was localized to osteoblasts apposed to bone or cartilage matrix; the intensity of expression correlated with matrix secretion. Chondroblasts and chondrocytes expressed lower but significant levels of TGF beta 1 mRNA; the expression was lost with the progression to calcifying cartilage. The three cytokines studied were differentially expressed both temporally and spatially, suggesting different roles for each in osteoblast and chondrocyte function.
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PMID:Expression of mRNA for IL1 beta, IL6 and TGF beta 1 in developing human bone and cartilage. 818 35

In three experimental models in rats, surgical construction of a self-filling blind loop (SFBL), trinitrobenzene sulfonic acid (TNB) -induced colitis, and the combination of SFBL and TNB, the hypothesis was studied that intestine-derived endotoxins play a role in the pathogenesis of hepatobiliary disorders in chronic inflammatory bowel disease (CIBD). After eight weeks of treatment, a mild increase in portal and systemic endotoxin levels and interleukin-6 concentrations was observed and the serum levels of alkaline phosphatase, bilirubin, and ALAT were only mildly increased in SFBL plus TNB rats. Histopathological examination of the liver showed hardly any abnormalities in all three rat models. These results show that low-grade portal and systemic endotoxinemia in rats, induced by bacterial overgrowth and/or chemical colitis, is not able to induce hepatobiliary alterations. To exclude definitively a possible role for portal endotoxinemia in the pathogenesis of CIBD-associated hepatobiliary abnormalities, however, an adequate animal model for CIBD is urgently needed.
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PMID:Experimental colitis in rats induces low-grade endotoxinemia without hepatobiliary abnormalities. 820 Feb 52

Interleukin-6 (IL-6) is a pluripotent cytokine which is made by osteoblasts, but its role in bone metabolism is uncertain. The aim of this study was to test the effect of IL-6 on bone formation in vitro using a nodule-forming assay. Osteoblast-enriched calvaria cells were isolated from 2-day-old Sprague-Dawley rats and cultured in the presence of 10(-8) M dexamethasone. After 2 days, calvaria cells were treated with recombinant human IL-6 for 72 h, washed and maintained for a further 18 days before fixation. IL-6 caused a dose-dependent inhibition of bone nodule formation, with a maximum reduction of 53% with 5000 U/ml IL-6. IL-6 also inhibited alkaline phosphatase activity in a dose-dependent manner (e.g. control: 114 +/- 9.2; IL-6: 68 +/- 10.6 nmol p-nitrophenol (pNP)/mg/min). IL-6 did not affect cell numbers during early cell growth up to 6 days but caused a small but significant reduction in cell number at confluence (8 days). These results demonstrate that IL-6 inhibits bone nodule formation by rat calvaria cells in vitro and suggest that IL-6 may inhibit osteoblast differentiation.
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PMID:Interleukin-6 inhibits bone formation in vitro. 832 17

Interleukin-4 (IL-4) modulates the activity of a variety of lymphoid, hemopoietic and mesenchymal cells, but little is known about its influence on bone cells. We have studied the effects of IL-4 on the human osteoblast-like cell line MG63. IL-4 (0.1-50 ng/ml) inhibited cell proliferation. The effect did not depend on cell density, but it was more marked in serum-free cultures than in the presence of serum. IL-4 also induced a dose-dependent increase in the expression of alkaline phosphatase stimulated by 1,25-dihydroxyvitamin D3, a marker of differentiated osteoblast activity. However, IL-4 did not modify the secretion of interleukin-6 or tumor necrosis factor. These results suggest that interleukin-4 may play a role as a modulator of osteoblast activity.
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PMID:Effects of interleukin-4 on human osteoblast-like cells. 832 20


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