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

Insulin-like growth factor binding proteins (IGF BP) and insulin-like growth factors (IGF) secretion by differentiating chondrocytes, derived from mouse embryonic limb bud and responsive to both IGF-I and -II [23], was investigated. The Western ligand blot analysis of the conditioned medium (CM) from days 1, 3, 5 and 7 of culture revealed the secretion of IGF BP of approx. 35-40, 28-30 and 24-26 kDa. The 35-40 kDa protein which comigrated with the 40 kDa protein in CM of trophoblast cells identified as IGF BP-3. The 28-30 kDa protein was identified as IGF BP-2 by Western immunoblotting with alpha-IGF BP-2 antisera. The 24-26 kDa protein was consistent with the nonglycosylated form of IGF BP-4. Secretion of three IGF BPs were increased with the age of the culture. This suggested that the major IGF BP secreted by differentiating chondrocytes in culture are IGF BP-2, -3 and -4. All three of these IGF BPs were stimulated by both IGF-I and -II. IGF-I was approx. 2-fold more potent than IGF-II. The investigation of the localized production of IGF revealed that chondrocytes, similar to IGF BP, secreted IGF-II in differentiation dependent manner. No IGF-I secretion was identified. Examination of the secretion of solubilized IGF-II receptor by the chondrocytes, in contrast to trophoblasts, failed to reveal the presence of IGF-II receptor in the CM. This suggested that, unlike many other cells, including trophoblasts, chondrocytes do not secrete solubilized IGF-II receptor. In summary, the present results suggested an interactive autocrine/paracrine action of IGF BP and IGF-II in the chondrocytes, while the IGF-I action is predominantly endocrine.
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PMID:Insulin-like growth factor (IGF) binding proteins and insulin-like growth factor secretion by cultured chondrocyte cells: identification, characterization and ontogeny during cell differentiation. 750 58

The synthesis and release of parathyroid hormone-related protein (PTHrP) could be influenced in a paracrine or autocrine manner by substances present around or inside tumours, such as bone or stromal cell-derived cytokines, factors produced by the tumour itself or by peritumoural inflammatory cells. We investigated the effects of various cytokines known to be synthesized by osteoblasts, stromal cells, leucocytes or cancer cells, on PTHrP production by the human lung squamous cell carcinoma line BEN. The influence of tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) was studied, and compared with those of insulin-like growth factors-I and -II (IGF-I, IGF-II), or macrophage- or granulocyte-macrophage colony-stimulating factors (M-CSF, GM-CSF). TNF-alpha caused a 1.9 +/- 0.1-fold increase in immunoreactive PTHrP production, which was maximal by 24 h of incubation. IL-6 caused a 2.3 +/- 0.2-fold increase, which was maximal by 16 h. These effects, which were time- and concentration-dependent, were blocked by monoclonal antibodies raised against the corresponding cytokine. An increase of PTHrP mRNA was found in IL-6-treated cells. IGF-I and IGF-II increased PTHrP production by 2.0 +/- 0.3- and 2.3 +/- 0.1-fold respectively. Neither M-CSF nor GM-CSF altered PTHrP production up to 64 h of incubation. PTHrP production was not affected by varying extracellular calcium concentrations, but was decreased by incubation with 100 nmol/l dexamethasone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of parathyroid hormone-related protein production in a human lung squamous cell carcinoma line. 782 96

We studied the effects of interleukin-6(IL-6) on DNA synthesis and cyclic AMP production in rat thyroid FRTL-5 cells. When cells were incubated with IL-6 in the presence or absence of IGF-I, cell proliferation was not observed. By contrast, IL-6 stimulated DNA synthesis in a dose dependent manner when TSH was added concomitantly. On the other hand, IL-6 did not modulate the cAMP accumulation in the presence or absence of TSH. These data demonstrate that, like IGF-I, IL-6 may be able to act as a growth factor through activation of a mitogenic signal transduction pathway different from A-kinase in FRTL-5 cells.
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PMID:Effect of interleukin-6 on cell proliferation of FRTL-5 cells. 838 10

We examined the massive early cell death that occurs in the ventral horn of the cervical spinal cord of the chick embryo between embryonic days 4 and 5 (E4 and E5). Studies with immunohistochemical, in situ hybridization, and retrograde-tracing methods revealed that many dying cells express Islet proteins and Lim-3 mRNA (motoneuron markers) and send their axons to the somatic region of the embryo before cell death. Together, these data strongly suggest that the dying cells are somatic motoneurons. Cervical motoneurons die by apoptosis and can be rescued by treatment with cycloheximide and actinomycin D. Counts by motoneuron numbers between E3.5 and E10 revealed that, in addition to cell death between E4 and E5, motoneuron death also occur between E6 and E10 in the cervical cord. Studies with [3H]thymidine autoradiography and morphological techniques revealed that in the early cell-death phase (E4-E5), genesis of motoneurons, axonal elongation, and innervation of muscles is still ongoing. However, studies with [3H]thymidine autoradiography also revealed that the cells dying between E4 and E5 become postmitotic before E3.5. Increased size of peripheral targets, treatment with neuromuscular blockade, and treatment with partially purified muscle or brain extracts and defined neurotropic agents, such as NGF, BDNF, neurotrophin-3, CNTF, bFGF, PDGF, S100-beta, activin, cholinergic differentiation factor/leukemia inhibitory factor, bone morphogenetic protein-2, IGF-I, interleukin-6, and TGF-beta 1, were all ineffective in rescuing motoneurons dying between E4 and E5. By contrast, motoneurons that undergo programmed cell death at later stages (E6-E10) in the cervical cord are target-dependent and respond to activity blockade and trophic factors. Experimental approaches revealed that early cell death also occurs in a notochord-induced ectopic supernumerary motoneuron column in the cervical cord. Transplantation of the cervical neural tube to other segmental regions failed to alter the early death of motoneurons, whereas transplantation of other segments to the cervical region failed to induce early motoneuron death. These results suggest that the mechanisms that regulate motoneuron death in the cervical spinal cord between E4 and E5 are independent of interactions with targets. Rather, this novel type of cell death seems to be determined by signals that either are cell-autonomous or are derived from other cells within the cervical neural tube.
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PMID:A novel type of programmed neuronal death in the cervical spinal cord of the chick embryo. 864 12

Interleukin-6 (IL-6), a cytokine produced by bone cells, is known to influence bone resorption by stimulating the development of osteoclasts from precursor cells and to have mitogenic actions on osteoblastic cells. Insulin-like growth factors (IGFs) are important local regulators of bone formation, and IGF binding protein (IGFBP)-5 stimulates bone cell growth and enhances the effects of IGF-I. We tested the effects of IL-6 in the presence and absence of its soluble receptor (sIL-6R) on IGFBP-5 expression in cultures of osteoblast-enriched cells from 22-day-old fetal rat calvariae (Ob cells). When tested individually, IL-6 and sIL-6R had a modest stimulatory effect on IGFBP-5 messenger RNA (mRNA) levels. In contrast, when IL-6 and sIL-6R were tested in combination, they caused a considerable increase in IGFBP-5 mRNA levels, and IL-6 at 100 ng/ml and sIL-6R at 125 ng/ml increased IGFBP-5 transcripts by 5- to 7-fold after 24 h. The effect of IL-6 and sIL-6R on IGFBP-5 transcripts was not blocked by indomethacin, but cycloheximide markedly inhibited IGFBP-5 mRNA levels in control and treated cultures. IL-6 and sIL-6R did not modify the decay of IGFBP-5 mRNA in transcriptionally arrested Ob cells, and stimulated the rate of IGFBP-5 transcription as demonstrated by a nuclear run-on assay. IL-6 and sIL-6R did not increase intact IGFBP-5 levels in the extracellular matrix and increased IGFBP-5 fragments in the culture medium. Conditioned medium from Ob cells induced the proteolytic fragmentation of an IGFBP-5 standard, an effect that was accelerated and enhanced by conditioned medium from IL-6/sIL-6R-treated cultures and prevented by metalloprotease inhibitors. In conclusion, IL-6, in the presence of sIL-6R, stimulates IGFBP-5 mRNA expression in Ob cells by transcriptional mechanisms, and accelerates the fragmentation of the protein.
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PMID:Interleukin-6 and its soluble receptor regulate the expression of insulin-like growth factor binding protein-5 in osteoblast cultures. 923 91

The purpose of the present study was to characterize the acute changes in the insulin-like growth factor (IGF) system in humans after administration of endotoxin (lipopolysaccharide; LPS). Escherichia coli LPS (4 ng/kg) was injected intravenously into healthy adults, and serial blood samples were collected for the next 5 h; subjects injected with saline served as time-matched controls. LPS administration resulted in a gradual decrease in the total extractable IGF-I concentration, which was reduced by approximately 20% over the final 2 h of the experiment; levels of free IGF-I were not significantly altered. LPS also produced a marked but transient elevation in growth hormone (GH) concentration. IGF-binding protein (BP)-1 levels were elevated more than fivefold 2 h after LPS injection, and thereafter levels gradually returned toward baseline. IGFBP-2 concentration also increased after LPS injection, but the maximal increase (approximately 50% above basal) was observed during the final 2 h of the protocol. In contrast, IGFBP-3 levels did not vary over the period examined in response to LPS, and there was no apparent increase in number of BP-3 proteolytic fragments. Cortisol levels were increased early and remained two- to threefold above baseline throughout the protocol. No significant alterations in serum concentration of glucose or insulin were noted. LPS also produced an early elevation in tumor necrosis factor and a later increase in interleukin-6. These data indicate that the acute changes in the GH-IGF axis in humans in response to LPS are comparable with those observed in humans in other traumatic conditions and in animal models of endotoxemia and infection.
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PMID:Acute alterations in growth hormone-insulin-like growth factor axis in humans injected with endotoxin. 924 74

The endogenous factors that underlie the transient induction of the gene encoding spermidine/spermine N1-acetyltransferase (SSAT), the rate-limiting enzyme in cellular polyamine catabolism, in pig uterine endometrium during periimplantation are not known. The present study examined a number of peptide growth factors and regulatory molecules that are present within the uterine environment at early pregnancy, coincident with maximal SSAT gene expression, for their ability to manifest endogenous SSAT gene-inducing activity. Basal SSAT expression in luminal epithelial cells was higher (p < 0. 01) than that for glandular epithelial (GE) or stromal (ST) cells. Recombinant human insulin-like growth factor-I (IGF-I; 50 ng/ml) had no effect on steady-state SSAT mRNA levels, but it increased mitogenesis in all three cell types. In contrast, IGF-I caused a marked induction (p < 0.01) of SSAT mRNA levels in the human endometrial carcinoma cell line Hec-1-A. Uterine explants incubated with interleukin-6, transforming growth factor alpha, epidermal growth factor (each at 1, 10, and 100 ng/ml), retinoic acid and retinol (each at 0.01, 0.1, and 1 microM), and estradiol-17beta (10 nM) had SSAT mRNA levels similar to controls. By contrast, leukemia inhibitory factor (LIF; at 10 and 100 ng/ml) caused a modest, but significant (p < 0.05), increase in SSAT mRNA levels over those of untreated explants. This effect of LIF, however, did not approach the level of induction observed in GE or ST cells after addition of medium conditioned by Day 12 or 17 porcine conceptuses and in endometrial explants supplemented with medium conditioned by Day 21 porcine conceptuses or a continuous cell line (Jag-1) derived from Day 14 porcine trophoblast. We suggest that transient induction of endometrial SSAT gene expression at implantation is mediated by the functional interactions of specific conceptus-derived regulatory factors, distinct from estrogen, with endometrial-derived factor(s) such as LIF. These complex interactions are probably requisite for the transient, yet dramatic, induction of SSAT gene expression and may be critical for successful implantation.
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PMID:Paracrine inducers of uterine endometrial spermidine/spermine N1-acetyltransferase gene expression during early pregnancy in the pig. 978 Mar 34

GH deficiency (GHD) is associated with increased prevalence of atherosclerosis and cardiovascular morbidity. Because monocytes play a crucial role in the development of atherosclerosis, we investigated in the present study the effect of GH deficiency and subsequent GH replacement on monocytic function in hypopituitary subjects. Twelve patients were randomized to receive GH replacement therapy (either 3 or 6 microg/kg x day, s.c.) for 3 months. Plasma levels and monocyte production of cytokines and monocyte adhesion to endothelium were determined in controls and patients with GHD before and after GH treatment. Before GH therapy, patients with GHD had increased basal plasma tumor necrosis factor-alpha (TNF alpha; 220% over control values; P = 0.004) and interleukin-6 (IL-6; 340% over control values; P 0.0009) levels. Basal monocyte production of both cytokines was also significantly higher in patients with GHD [484% over control values for TNF alpha (P = 0.0007); 1479% over control values for IL-6 (P = 0.035)]. GH treatment for 3 months led to a reduction in plasma TNF alpha (135% over control values; P = 0.03, pre- vs. post-GH therapy), monocyte TNF alpha production (204% over control values; P = 0.01), plasma IL-6 (219% over control values; P = 0.07), and monocyte IL-6 production (448% over control values; P = 0.01). Plasma TNF alpha levels positively correlated with monocyte TNF alpha production in patients with GHD both before and after GH therapy (P = 0.003 and P = 0.049, respectively). A positive correlation (P = 0.0003) was also observed between monocyte TNF alpha production and monocyte IL-6 production. There were no correlations between these plasma cytokine levels or monocyte cytokine production and parameters of body composition, lipid profile, or IGF-I and IGF-binding protein-3 levels. Before GH treatment, adhesiveness of monocytes to cultured aortic endothelial cells was also enhanced. This alteration was not reversed by GH administration. In conclusion, our results demonstrate that markers of monocyte activation are increased in patients with GHD and that GH replacement partly reduces these abnormalities. Reduction of cellular activation of monocytes by GH therapy could potentially contribute to reduce the risk of cardiovascular events in patients with GHD.
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PMID:Alterations of monocyte function in patients with growth hormone (GH) deficiency: effect of substitutive GH therapy. 1048 24

A genetic contribution to bone mass determination was first described in the early 70s. Elucidation of gene contribution to this has since been attempted through studies analyzing associations between bone mass acquisition and/or maintenance and polymorphic variations of several genes. The first to be described was the vitamin D receptor gene (VDR), initially claimed to contribute to almost 75% of the genetic variation in bone mineral density (BMD) in twin and general population studies. Not all of the studies published to date conclude that a clear relationship exists between polymorphic VDR alleles and BMD, and the molecular basis for the VDR gene polymorphisms influence on bone mineralization has not yet been clarified. Since then, other genes with a significant role in bone metabolism such as estradiol receptor, collagen type 1alpha1, TGF-beta1, interleukin-6, calcitonin receptor, alpha2-HS-glycoprotein, osteocalcin, calcium-sensing receptor, interleukin-1 receptor antagonist, beta3-adrenergic receptor, apolipoprotein E, PTH, IGF-I and glucocorticoid receptor have been analyzed. Some polymorphic variations in these genes have been associated in some works with significant differences in BMD, with even more significant contributions when associations of different gene polymorphisms were analyzed. Again, the molecular basis for the contribution of these alleles to bone mass determination has not yet been described. A different approach has been attempted by linkage analysis of loci involved in bone density in pedigrees with low BMD using BMD as a quantitative trait. Recent results do not confirm, in these families, any association with any of the previously reported genes, but rather with other as yet unidentified genes. The genetic contribution to mild variations in the general population, as a result of environmental and endogenous individual influences, probably differs completely from that providing a pathologic BMD.
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PMID:Genetic determinants of bone mass. 1046 Oct 16

The objective of this study was to assess the influence of specific factors on post-thaw development of mouse cryopreserved morulae. Thawed morulae (n = 206) were randomly distributed between 10 treatment groups: medium alone control (CT), Vero (VR) cells, leukaemia inhibitory factor (1 ng/ml), interleukin-6 (1 ng/ml), transforming growth factor (TGF) alpha (2 ng/ml), epidermal growth factor (EGF) (4 ng/ml), platelet-derived growth factor (1 ng/ml), insulin-like growth factor (IGF)-I (30 ng/ml), IGF-II (1 ng/ml) and TGFbeta (2 ng/ml). At 4, 8, 20, 30 and 48 h, a digitized image of each thawed embryo was captured and stored for later analysis. The following parameters were examined: blastocoel formation, blastocyst expansion, zona thickness and hatching. At termination of the experiment, cell number per embryo was determined by bisbenzimide staining. When contrasted to the medium alone control, co-culture consistently accelerated the development of frozen-thawed morulae to the hatched blastocyst stage, allowing embryos to recover rapidly from any damage sustained during the cryopreservation process. While no single growth factor/cytokine was able to completely mimic the results achieved with co-culture, all of the growth factors impacted positively on at least one of the morphological parameters studied. Cell proliferation was significantly stimulated by just 48 h exposure to growth factors, either through co-culture or by direct media supplementation. Co-culture again yielded the best results with a mean cell count of 217 +/- 76 cells per blastocyst as compared with 131 +/- 36 in control medium alone. Amongst the factors tested, IGF-I, IGF-II and EGF had the greatest impact, with mean cell counts of 172 +/- 50, 168 +/- 50 and 179 +/- 55 respectively. Whereas only 5% of CT embryos developed to blastocysts with > 200 cells, 51% of thawed embryos placed on co-culture monolayers and 25-32% of embryos cultured with IGF-I, IGF-II or EGF had > 200 cells. This study for the first time systematically describes the effect of culture regimen and growth factor additives on the post-thaw development of cryopreserved embryos.
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PMID:Assessment of growth factor effects on post-thaw development of cryopreserved mouse morulae to the blastocyst stage. 1065 14


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