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)

Using a functioning rat thyroid cell line (FRTL-5), we examined the effects of some cytokines, particularly interleukin-1 (IL-1) on the growth of thyroid cells. In 5H medium, namely Coon's modified Ham's F-12 medium supplemented with 5% calf serum and a five-hormone preparation consisting of insulin, hydrocortisone, transferrin, glycyl-L-histidyl-L-lysine acetate and somatostatin, IL-1 enhanced the growth of FRTL-5 cells detected by [3H]TdR incorporation. However, in 6H medium (5H medium plus bovine TSH), IL-1 inhibited the growth of FRTL-5 cells. Both effects were neutralized by the addition of anti-IL-1 antibody. Furthermore, IL-1 inhibited the growth of FRTL-5 cells induced by forskolin which is known as an adenylate cyclase activator. FRTL-5 cells have specific IL-1 receptors detected by the binding of 125I-labeled IL-1 alpha. By Scatchard plot analysis, the numbers and the dissociation constants of IL-1 receptors on FRTL-5 cells were shown to be 5225/cell and 8.69 x 10(-10) M. Interleukin-2, interleukin-6 and interferon-gamma (IFN-gamma) had no significant effects on the cell growth in 6H medium, while IFN-gamma and insulin-like growth factor I stimulated cell growth somewhat in 5H medium. These results suggest that IL-1 plays a regulatory role in the growth of thyroid cells through binding to the IL-1 receptors.
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PMID:Inhibitory effect of IL-1 on the TSH dependent growth of rat thyroid cells (FRTL-5). 212 71

The intrathyroidal production of Interferon gamma, tumour necrosis factor alpha and beta, Interleukin-1 alpha and beta, Interleukin-6, platelet-derived growth factor A and of transforming growth factor-beta was analysed in patients with autoimmune and non-autoimmune thyroid disease. Cytokines were assessed indirectly by slot blot mRNA analysis in fresh tissue samples (unpurified cells, infiltrating mononuclear cells and thyroid follicular cells), in thyroid follicular cells in primary culture, as well as in thyroid-derived T-cell clones. The production of Interleukin-1 alpha and beta, Interleukin-6 and transforming growth factor beta was additionally measured by bioassay. Cytokine production by thyroid-infiltrating mononuclear cells generally did not differ between autoimmune and non-autoimmune samples, the whole panel of all cytokines being found in freshly purified cells as well as in thyroid-derived T-cell clones from patient with Graves' disease, as well as with multinodular non-toxic goitre. Thyroid follicular cells produced Interleukin-1 alpha, Interleukin-6 and transforming growth factor beta. Interleukin-1 and Interleukin-6 production did not differ between thyroid follicular cells from autoimmune and non-autoimmune thyroids. Transforming growth factor beta was, however, lower in non-toxic goitre than in Graves' disease and in normal thyroid tissue, but could be increased by exposure of the cells to micromolar concentrations of iodide. This seemed of special interest, as transforming growth factor beta proved to inhibit thyroid follicular cell growth in response to known growth stimuli, such as insulin-like growth factor I or epidermal growth factor.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intrathyroidal cytokine production in thyroid disease. 267 71

In the past decade, cytokines came into focus as important multifunctional mediators regulating cellular functioning and intercellular connections. Particular cytokines may both inhibit and stimulate cells playing an important role in maintaining homeostasis of the normal tissue. In the majority of pathologies not individual cytokines but their complexes are involved. Numerous studies on cytokines are mainly aimed at evaluating the role of the following cytokines in pulmonary diseases: tumour necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta), insulin-like growth factor I (IGF-I), interleukin-1 (IL-1), and recently interleukin-6 (IL-6). The possible physiologic significance and role of cytokines in lung diseases are surveyed.
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PMID:[Biological properties of cytokines and their role in lung pathology]. 841 54

Cytokines and growth factors are important in bone tissue as mediators of cell-to-cell and matrix-to-cell communication. Cytokines also locally mediate the effects of several hormones on bone cells. Indeed, calciotropic hormones modulate the bone-cell production rate of these factors and, conversely, can change the number of receptors for these hormones on bone cells. Most cytokines are active in bone, but the existence of a bone-specific cytokine is still questioned. Recent work has searched for estradiol modulation of osteoblastic cytokine acting on osteoclast differentiation. In mice, increased interleukin-6 production by osteoblasts is responsible for increased bone resorption occurring after ovariectomy. Interleukin-6 could also be an autocrine or paracrine factor in the pathogenesis of increased resorption occurring in giant cell tumor or in Paget's disease. During osteoporosis and age-related bone changes, modifications of the production of insulin-like growth factor I or of one of its binding proteins could be responsible for low bone formation. Interrelationships between cytokines and hormones can affect the action of parathyroid hormone-related peptide on bone cells. The field of implication of cytokines in metabolic bone disease is growing.
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PMID:Bone cytokines. 851 70

The coupling of isoelectric focusing on immobilized pH gradients (IPG) with electrospray-mass spectrometry (ES-MS) was applied to the characterization of proteins according to two different and important properties, such as net surface charge and molecular mass. From a technical point of view, these methods are complementary, since ES-MS requires ion-free samples as usually supplied by isoelectric focusing on IPGs. This report describes the experiments carried out on model proteins to demonstrate the feasibility of the sequential application of these two techniques for the characterization of proteins. A minimum of 5 micrograms protein was needed for good signal by mass spectrometry. The following proteins were studied: myoglobin, truncated interleukin-6-mutein, recombinant cytochrome c551 and insulin-like growth factor I. Extraction from the IPG matrix was carried out in 70% acetonitrile/30% water/0.05% trifluoroacetic acid either by passive diffusion or by centrifugation through a 0.22 micron Amicon membrane, with protein recoveries of 80-85%.
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PMID:Characterization of proteins by sequential isoelectric focusing on immobilized pH gradients and electrospray mass spectrometry. 852 1

Renewal of the bone matrix is induced by bone cells called osteoblasts and osteoclasts, which act sequentially on the bone surface. This "remodelling" depends on local factors, such as cytokines and growth factors which play an important role in the bone tissue as mediators of cell-to-cell and matrix-to-cell communication. Growth factors released from the bone matrix during the resorption are responsible for the refilling of the resorption cavity by osteoblasts. Cytokines also mediate locally the effect of several hormones on bone cells. Recent work is concerned with the modulation by oestradiol of osteoblastic cytokines acting on osteoclast differentiation. In mice, an increased production of interleukin-6 production by osteoblasts is responsible for the increased bone resorption occurring after ovariectomy. Other growth factors, such as transforming growth factor-beta, whose secretion is modified by oestradiol, may also be implicated. In women, an increase in cytokine production by blood mononuclear cells is associated with the occurence of menopause and reversed by oestrogen treatment. During osteoporosis and age-related bone changes, changes in the production of insulin-like growth factor I or of one of its binding proteins could be responsible for low bone formation. In addition to their role in bone remodelling, cytokines and growth factors are now implicated in osteoporosis.
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PMID:Dynamics of bone remodelling: biochemical and pathophysiological basis. 889 25

It has become evident that apoptosis, an active form of cell 'suicide', plays an important role in the normal function of all tissues. A balance of cell proliferation and apoptosis is maintained in a healthy individual and any imbalance of the two processes could lead to pathological changes. In both sexes, massive apoptosis accounts for the demise of a majority of gonadal cells (ovarian granulosa cells and male germ cells) during reproductive life. Recent studies have indicated the important role of gonadotrophins as survival factors in both the ovary and the testis. Furthermore, intra-gonadal survival. factors in the ovary (oestrogens, insulin-like growth factor I, epidermal growth factor, basic fibroblast growth factor, interleukin-1 beta, nitric oxide, etc.) and testis (androgens) have been shown to act in concert with the gonadotrophins. In contrast, several apoptotic factors (androgens, gonadotrophin-releasing hormone-like peptide and interleukin-6) may be important in inducing the demise of ovarian follicles. Understanding of the hormonal and cellular mechanisms responsible for gonadal cell apoptosis will provide new approaches for the treatment of gonadal degenerative conditions such as premature ovarian failure and cryptorchidism, as well as for the design of new contraceptive approaches.
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PMID:Gonadal cell apoptosis: hormone-regulated cell demise. 907 7

1. Keratinocytes are functionally divided into stem cells, transit amplifying cells and terminally differentiated cells. In a hyperproliferative skin disease, psoriasis, increased mitotic activity of the stem cells is chiefly responsible for epidermal hyperplasia. The effects of 1,25dihydroxyvitamin D3 (1,25(OH)2D3) and potent vitamin D3 analogues (MC 1288: 20-epi-1,25(OH)2D3, MC 1301: 20-epi-24a-homo-26,27-dimethyl-1,25(OH)2D3, KH 1060: 20-epi-22-oxa-24a-homo-26,27-dimethyl-1,25(OH)2D3) on the stem cells were investigated. 2. Stem cells were identified retrospectively as those giving rise to large keratinocyte colonies in culture (holoclones). 1,25(OH)2D3 (10(-8)-10(-6) M) suppressed formation of holoclones by stimulating the progenitor cell differentiation into the phenotype expressing differentiation markers (keratins K1/K10 and involucrin). 3. 20-Epi vitamin D3 analogues were more potent than 1,25(OH)2D3 in inhibiting the clonal keratinocyte growth. This activity correlated with the ability to induce cell differentiation (KH 1060 > MC 1301 > MC 1288 > 1,25(OH)2D3). 4. Cytokines modulated the effects of 1,25(OH)2D3 on clonal growth. One of the following cytokines (epidermal growth factor, transforming growth factor alpha, interleukin-1 alpha, interleukin-1 beta, interleukin-6, interleukin-8) was required for 1,25(OH)2D3 to suppress clonal growth and induce cell differentiation. In contrast, keratinocyte growth factor and insulin-like growth factor I attenuated the effects of 1,25(OH)2D3. 5. In conclusion, 1,25(OH)2D3 and 20-epi vitamin D3 analogues suppress clonal growth by directly inducing the differentiation of progenitor cells. It is conceivable that stimulation of stem cells differentiation is a major mechanism of action of vitamin D3 compounds in psoriasis. Balance between different types of cytokines in psoriatic epidermis may be an important factor determining the clinical effect of vitamin D-based therapy.
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PMID:Effects of 1,25-dihydroxyvitamin D3 and its 20-epi analogues (MC 1288, MC 1301, KH 1060), on clonal keratinocyte growth: evidence for differentiation of keratinocyte stem cells and analysis of the modulatory effects of cytokines. 913 25

A male patient with abnormal postpubertal bone elongation was shown earlier to have a mutation in both alleles of the estrogen receptor, resulting in a nonfunctional gene. Marrow stromal fibroblasts (MSFs) derived from this patient were called HERKOs (human estrogen receptor knock outs), and in order to obtain continuous HERKO cell lines, they were immortalized using a recombinant adenovirus-origin-minus SV40 virus. MSFs are unique cells because they support hematopoesis and contain a mixed population of precursor cells for bone, cartilage, and fat. Three established cell lines (HERKO2, HERKO4, and HERKO7) were characterized and compared with the heterogeneous population of nonimmortalized HERKOs for their osteogenic potential. We performed Northern analysis of matrix genes implicated in bone development and metabolism and an in vivo bone formation assay by transplanting the cells subcutaneously into immunodeficient mice. All three HERKO lines expressed high amounts of collagen 1A1, osteopontin, osteonectin, fibronectin, decorin, biglycan, and alkaline phosphatase. Except for osteopontin, expression of these genes was slightly lower compared with nonimmortalized HERKOs. In the in vivo bone formation assay, the heterogeneous population of nonimmortalized HERKOs formed bone with high efficiency, while the HERKO lines induced a high-density, bone-like matrix. Finally, all HERKO cell types secreted high levels of insulin-like growth factor I and interleukin-6 into the culture medium relative to cells of normal human subjects. In summary, these lines of HERKO cells retain several of the phenotypic traits of MSFs after immortalization, including matrix and cytokine production, and provide a valuable source of a unique human material for future studies involving estrogen action in bone and bone marrow metabolism.
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PMID:Immortalization and characterization of bone marrow stromal fibroblasts from a patient with a loss of function mutation in the estrogen receptor-alpha gene. 955 60

To evaluate whether interferon-gamma (IFN-gamma) is involved in the interaction between the immune and endocrine systems in vivo, we studied six healthy subjects twice in a placebo-controlled trial: once after administration of recombinant human IFN-gamma and, on another occasion, after administration of saline. The rate of appearance of glucose was determined by infusion of [6,6-2H2]glucose and resting energy expenditure by indirect calorimetry. Human leukocyte antigen-DR gene expression on monocytes and serum neopterin increased after administration of IFN-gamma (P < 0.05 vs. control). IFN-gamma increased serum interleukin-6 levels significantly. Levels of tumor necrosis factor-alpha remained below detection limits. IFN-gamma increased plasma concentrations of ACTH and cortisol (P < 0.05 vs. control), IFN-gamma did not alter concentrations of growth hormone, (nor)epinephrine, insulin, C peptide, glucagon, or insulin-like growth factor I. IFN-gamma did not alter plasma concentrations of glucose and free fatty acids nor the rate of appearance of glucose. IFN-gamma increased resting energy expenditure significantly. We conclude that IFN-gamma is a minor stimulator of the endocrine and metabolic pathways. Therefore, IFN-gamma by itself is probably not a major mediator in the interaction between the immune and the endocrine and metabolic systems.
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PMID:Interferon-gamma has immunomodulatory effects with minor endocrine and metabolic effects in humans. 993 Nov 85


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