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)

Insulin-like growth factor-I (IGF-I) is a potent stimulator of bone formation. Whether this growth factor also induces bone resorption has not been studied in detail. We used two organ culture systems to examine the direct effect of IGF-I on bone resorption. Fetal mouse radii/ulnae, containing mature osteoclasts, showed no response to IGF-I, indicating that osteoclastic activity is not influenced by IGF-I. Fetal mouse metacarpals/metatarsals, containing just osteoclast precursors and progenitors, showed an increase in resorption in response to IGF-I, indicating that IGF-I stimulates the formulation of osteoclast precursors/progenitors and thereby increases the number of osteoclasts. Interleukin-6 (IL-6) has been hypothesized to be a mediator of bone resorptive agents such as parathyroid hormone (PTH). Both radii/ulnae and metacarpals/metatarsals reacted to IGF-I with an increase in IL-6 production. IL-6 production by UMR-106 osteogenic osteosarcoma cells was positively modulated by IGF-I, indicating that osteoblasts are likely to be the cells responsible for increased IL-6 production by the bones, and that IL-6 might be a mediatory of IGF-I-stimulated bone resorption.
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PMID:Osteoclast formation together with interleukin-6 production in mouse long bones is increased by insulin-like growth factor-I. 156 29

The expression of insulin-like growth factor-I (IGF-I), interleukin-6 (IL-6), and transforming growth factor-beta 1 (TGF-beta 1) mRNA in rat femurs was examined following marrow ablation. Northern blot analysis showed multiple transcripts of IGF-I, a major transcript of 1.3 kb and a minor one of 2.4 kb for IL-6 and a single band of 2.5 kb for TGF-beta 1, respectively. Examination of the temporal activation pattern showed IGF-I expression peaked at day 3 (150% over the basal level) after injury and preceded the maximal expression of procollagen alpha 1(I), osteopontin, alkaline phosphatase, and osteocalcin mRNAs. This suggests that IGF-I is involved mainly in osteoblast development and bone formation. In contrast, IL-6 expression was elevated between days 3 and 9 (45-60% over the basal level). The sustained elevation of IL-6 expression at day 9 is consistent with the role for this cytokine in the development of osteoclasts and bone resorption. The expression of TGF-beta 1 was not altered up to day 9 after marrow ablation. While the temporal expression patterns of IGF-I and IL-6 mRNA did not differ between adult and old rats, the maximal level of IGF-I mRNA at day 3 was 72% higher in adult as compared to old bones. In contrast, the peak level of IL-6 mRNA at days 6-9 was 45% higher in old as compared to adult bones. Although the level of TGF-beta 1 mRNA did not change following marrow ablation, levels of TGF-beta 1 were consistently higher in old rats. Our results suggest that the impaired bone formation and elevated bone resorption in aged animals may be due in part to the reduced expression of IGF-I and an overexpression of IL-6 in old bone.
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PMID:Effect of age on the expression of insulin-like growth factor-I, interleukin-6, and transforming growth factor-beta mRNAs in rat femurs following marrow ablation. 873 6

We have studied the production of interleukin-11 (Il-11) in 13 breast cancer cell (BCC) lines. Two of these cell lines (MDA-MB-231 and Hs578T) expressed the cytokine at both the protein and mRNA levels. Il-11 did not modulate the growth of five BCC lines examined, including the two cytokine-producing BCC lines. The production of Il-11 was increased by transforming growth factor-beta1 in a dose-dependent manner with a rapid (2 h) and transient (24 h) mRNA induction, but not by epidermal growth factor, insulin-like growth factor-I and -II, basic fibroblast growth factor, platelet-derived growth factor or parathyroid hormone. The cyclic AMP inducer, forskolin, and the activator of protein kinase C, phorbol 12-myristate 13-acetate, also stimulated the production of Il-11. Besides Il-11, MDA-MB-231 and Hs578T were the only BCC lines to produce interleukin-6 (Il-6) protein and mRNA. Since Il-11 and Il-6 are potent stimulators of osteoclast development and bone is a major source of TGF-beta1, our data suggest that Il-11, together with Il-6, contributes to the high bone destructive capacity of MDA-MB-231 cells and could play a role in breast cancer-induced osteolysis.
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PMID:Production and regulation of interleukin-11 by breast cancer cells. 961 55

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

Somatostatin and its analogs can inhibit growth in several cell types, in part by interfering with insulin-like growth factor-I (IGF-I) signaling. Our previous studies point to the importance of paracrine and autocrine IGF-I in the support of growth and survival of human multiple myeloma (MM) cell lines. In this report, we have investigated the potential role of a somatostatin analog, octreotide, in regulating growth and/or survival in MM. The results show that all MM cell lines express functional somatostatin receptors (sst). The MM cell lines express the subtypes sst2, sst3, and predominantly sst5 as determined by reverse-transcriptase polymerase chain reaction and fluorescence-activated cell sorter analysis. Octreotide inhibited the growth of both the interleukin-6 (IL-6)-dependent and the IL-6-independent MM cell lines. The effect is mainly cytostatic, resulting in 25% to 45% growth inhibition, and in three of eight of the MM cell lines a weak induction of apoptosis was recorded. Our results also show that octreotide may act as an inducer of apoptosis in primary B-B4(+) plasma cells isolated from bone marrow of MM patients. In conclusion, the results show a novel pathway for growth inhibition of MM cells: the activation of somatostatin receptor signaling.
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PMID:The somatostatin analog octreotide inhibits growth of interleukin-6 (IL-6)-dependent and IL-6-independent human multiple myeloma cell lines. 1002 2

The aim of the present study was to investigate, in human lung cancer, the relationship between weight loss and the existence of a low body cell mass (BCM) on the one hand, and the putative presence of systemic inflammation, an increased acute-phase response, anorexia, hypermetabolism and changes in circulating levels of several anabolic and catabolic hormones on the other. In 20 male lung cancer patients, pre-stratified by weight loss of >/=10% (n=10) or of <10% (n=10), the following measurements were performed: BCM (by dual-energy X-ray absorptiometry/bromide dilution), circulating levels of sTNF-R55 and sTNF-R75 (soluble tumour necrosis factor receptors of molecular masses 55 and 75 kDa respectively), interleukin-6, lipopolysaccharide-binding protein, albumin, appetite (scale of 0-10), resting energy expenditure (by indirect calorimetry) and circulating levels of catabolic (cortisol) and anabolic [testosterone, insulin-like growth factor-I (IGF-I)] hormones. Compared with the patients with a weight loss of <10%, those with a weight loss of >/=10% were characterized by higher levels of sTNF-R55 (trend towards significance; P=0.06), and lower levels of albumin (27.4 compared with 34.4 mmol/l; P=0.02), testosterone (13.2 compared with 21.5 nmol/l; P=0.01) and IGF-I (119 compared with 184 ng/ml; P=0.004). In the patient group as a whole, the percentage weight loss was significantly correlated with sTNF-R55 (r=0.59, P=0.02), albumin (r=-0.63, P=0.006) and IGF-I (r=-0.50, P=0.02) levels. Height-adjusted BCM was significantly correlated with sTNF-R55 (r=-0.57, P=0.03), sTNF-R75 (r=-0.50, P=0. 04), lipopolysaccharide-binding protein (r=-0.50, P=0.04), albumin (r=0.56, P=0.02) and resting energy expenditure/BCM (r=-0.54, P=0. 03), and there was a trend towards a correlation with IGF-I concentration (r=0.44, P=0.06). We conclude that, in human lung cancer, weight loss and the presence of a low BCM are associated with systemic inflammation, an increased acute-phase response and decreased levels of IGF-I. In addition, a decreased BCM is associated with hypermetabolism.
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PMID:Weight loss and low body cell mass in males with lung cancer: relationship with systemic inflammation, acute-phase response, resting energy expenditure, and catabolic and anabolic hormones. 1040 77

Sarcopenia is a term utilized to define the loss of muscle mass and strength that occurs with aging. Sarcopenia is believed to play a major role in the pathogenesis of frailty and functional impairment that occurs with old age. Progressive muscle wasting occurs with aging. The prevalence of clinically significant sarcopenia is estimated to range from 8.8% in young old women to 17.5% in old old men. Persons who are obese and sarcopenic (the "fat frail") have worse outcomes than those who are sarcopenic and non-obese. There is a disproportionate atrophy of type IIa muscle fibers with aging. There is also evidence of an age-related decrease in the synthesis rate of myosin heavy chain proteins, the major anabolic protein. Motor units innervating muscle decline with aging, and there is increased irregularity of muscle unit firing. There are indications that cytokines-especially interleukin-1beta, tumor necrosis factor-alpha, and interleukin-6-play a role in the pathogenesis of sarcopenia. Similarly, the decline in anabolic hormones-namely, testosterone, dehydroepiandrosterone growth hormone, and insulin-like growth factor-I-is also implicated in the sarcopenic process. The role of the physiologic anorexia of aging remains to be determined. Decreased physical activity with aging appears to be the key factor involved in producing sarcopenia. An increased research emphasis on the factors involved in the pathogenesis of sarcopenia is needed.
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PMID:Sarcopenia. 1128 18

Some cytokines, i.e. tumor necrosis factor-, interleukin-6 and soluble interleukin-2 receptors are associated with complications of stem cell transplantation. Insulin-like growth factors (IGFs) are a family of peptides essential for the proliferation of normal and malignant cells. Recently increased levels of IGFs have been associated with the development of malignant tumors. In this communication we report on 96 measurements of insulin-like growth factor-I (IGF-1), insulin-like growth factor-II (IGF-2), and insulin-like growth factor-binding protein-3 (IGFBP-3) performed in 19 patients following stem cell transplants. Seventeen patients had allogeneic and 2 patients autologous transplants. Most IGF determinations were made at days 0, 7, 14, 21 and 28, some at other time points. The baseline values (day 0) of IGF-1 and IGFBP-3 were not different from controls. IGF-2 values were slightly lower than controls. Following transplantation, a consistent increase of IGF-1 was observed in 9/16 patients at days 7 and 14. Later the values decreased again. IGF-2 and IGFBP-3 did not change significantly after transplantation. No direct correlation could be established with the severity of graft-versus-host disease, levels of interleukin-6 and the time to hematopoietic recovery. A potential relevance of IGFs following stem cell transplantation may be the early diagnosis of liver damage and the development of second malignancies. More studies are necessary to investigate the pathophysiology and the clinical relevance of the increase of IGF-1 following stem cell transplantation.
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PMID:Levels of insulin-like growth factor after stem cell transplantation. 1130 31

The erosion of lean body mass resulting from protracted critical illness remains a significant risk factor for increased morbidity and mortality in this patient population. Previous studies have documented the well known impairment in nitrogen balance results from both an increase in muscle protein degradation as well as a decreased rate of both myofibrillar and sacroplasmic protein synthesis. This protein imbalance may be caused by an increased presence or activity of various catabolic agents, such as tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6 or glucocorticoids, or may be mediated via a decreased concentration or responsiveness to various anabolic hormones, such as growth hormone or insulin-like growth factor-I. This review focuses on recent developments pertaining to the importance of alterations in the growth hormone-insulin-like growth factor-I axis as a mechanism for the observed defects in muscle protein balance.
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PMID:Role of growth hormone, insulin-like growth factor-I, and insulin-like growth factor binding proteins in the catabolic response to injury and infection. 1195 52

Recently we found that interleukin-6 (IL-6) knockout mice develop mature-onset obesity and that a single intracerebroventricular (ICV) injection of IL-6 increases energy expenditure. In the present study we investigated if chronic ICV treatment with IL-6 can suppress body fat mass. IL-6 was injected ICV daily for two weeks to rats fed a high-fat diet. IL-6 treatment but not saline treatment decreased body weight by 8.4% and decreased the relative weights of mesenteric and retroperitoneal fat pads. Consistent with this, circulating leptin levels were decreased by 40% after IL-6 treatment but not after saline treatment. Average food intake per day was decreased in the IL-6 treated group compared to the saline treated rats. IL-6 treatment did not change hepatic expression of the acute-phase protein haptoglobin, serum levels of insulin or insulin-like growth factor-I, or the weights of the heart, liver, kidneys, adrenals, and spleen. We conclude that centrally administered IL-6 can decrease body fat in rats without causing acute-phase reaction.
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PMID:Intracerebroventricular interleukin-6 treatment decreases body fat in rats. 1205 38


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