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)

Previously, we showed that several minor macromolecular glycolipids accounting for less than 5% of the lipoteichoic acid (LTA) fraction from Enterococcus hirae ATCC 9790 possess cytokine-inducing activity, whereas the purified LTA does not. In other words, the immunobiological activity of the LTA fraction reported in the 1980s was not attributable to LTA itself, but to other glycolipids coexisting in the fraction. In the present study, we improved the procedure of separation of the active glycolipids and evaluated their effects on cellular activation. The immunobiologically active glycolipids were separated from the crude glycolipid fraction obtained by hot phenol-water extraction of the cells. The total yield of active glycolipids was about fivefold higher than that separated by the previous method. Interleukin-6-inducing activities of the active glycolipids from 1,25-dihydroxy vitamin D(3)-differentiated human monocytic leukemia cells, THP-1, were inhibited by anti-CD14 mAbs in a dose-dependent manner. Macrophages from Toll-like receptor (TLR)-2-deficient or -4-deficient mice completely lacked the ability to produce tumor necrosis factor-alpha on stimulation with active glycolipids. These observations indicated that the cellular activation by the active glycolipids from E. hirae is mediated by CD14 and by both TLR2 and TLR4.
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PMID:Cytokine-inducing macromolecular glycolipids from Enterococcus hirae: improved method for separation and analysis of its effects on cellular activation. 1087 80

The mortality rate in hemodialysis patients remains extremely high, and reduced serum albumin concentration resulting from malnutrition is the strongest predictor of mortality and morbidity. Several inflammatory cytokines involved in malnutrition, including interleukin-1, interleukin-6, and tumor necrosis factor-alpha, are modulated by 1,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)], of which synthesis is impaired in end-stage renal disease. We evaluated whether 1,25-(OH)(2)D(3) deficiency might be involved in reduced serum albumin concentrations. Fifty-one predialysis uremic patients about to begin hemodialysis therapy were divided into groups with serum 1,25-(OH)(2)D(3) concentrations less than 18 pg/mL (low-D(3) group; n = 39) and concentrations of 18 pg/mL or greater (normal-D(3) group; n = 12). Serum albumin concentrations before the initiation of hemodialysis treatment were compared between the two groups. Furthermore, the effect of supplementation with active forms of vitamin D during 4 months of hemodialysis treatment on serum albumin concentrations was retrospectively evaluated in the low-D(3) group. Serum albumin concentrations in the low-D(3) group were significantly less than those in the normal-D(3) group (3.58 +/- 0. 50 versus 3.82 +/- 0.10 g/dL; P = 0.034). Considering all patients, a significant positive correlation between serum concentrations of albumin and 1,25-(OH)(2)D(3) was noted (r = 0.417; P = 0.0023). Supplementation with active forms of vitamin D significantly increased serum albumin concentrations in the low-D(3) group from 3. 61 +/- 0.12 to 3.79 +/- 0.13 g/dL (P = 0.0067). These findings indicate that reductions in serum albumin concentrations may be attributed, at least in part, to vitamin D deficiency in patients with end-stage renal disease.
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PMID:Vitamin D deficiency is implicated in reduced serum albumin concentrations in patients with end-stage renal disease. 1092 12

Paricalcitol (19-nor-1,25-dihydroxyvitamin D(2)), a new vitamin D analogue, recently became available for the treatment of hyperparathyroidism in patients with end-stage renal disease. It is safe and effective in suppressing parathyroid hormone, with apparently less propensity for hypercalcemia than calcitriol (1, 25-dihydroxyvitamin D(3)). However, the mechanism of action on bone has not been fully elucidated. This study compares the effects of paricalcitol and calcitriol on the bone mineral. Neonatal (5- to 7-day-old) mouse calvariae were incubated in the absence or presence of either paricalcitol or calcitriol for 48 hours, and calcium flux, osteocalcin and acid and alkaline phosphatase activity, and interleukin-6 (IL-6) release were determined. Increasing concentrations of both calcitriol and paricalcitol increased calcium efflux. At lower concentrations, paricalcitol had no effect on acid phosphatase activity; however, at 10(-8) mol/L, paricalcitol caused a significant increase similar to that of calcitriol at 10(-9) mol/L. Increasing concentrations of paricalcitol had no effect on alkaline phosphatase activity, whereas calcitriol (10(-8) mol/L) caused significant inhibition. At low concentrations, paricalcitol had no effect on osteocalcin release; however, at 10(-8) mol/L, both compounds significantly increased osteocalcin production. Neither compound had an effect on IL-6 release. These data show that: (1) at low concentrations, both compounds induce a similar calcium efflux from cultured bone; (2) at low concentrations, paricalcitol has no effect on osteocalcin or acid and alkaline phosphatase activity; (3) at greater concentrations, paricalcitol and calcitriol have similar effects on acid phosphatase and osteocalcin activity; (4) calcitriol, but not paricalcitol, inhibits alkaline phosphatase release; and (5) the bone-resorbing effect of both compounds is independent of IL-6 release. Thus, although both compounds have similar effects on calcium efflux from bone, at therapeutic concentrations, paricalcitol does not seem to inhibit osteoblast activity. This may explain, in part, the lower calcemic effect of paricalcitol.
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PMID:Effect of the vitamin D analogues paricalcitol and calcitriol on bone mineral in vitro. 1100 82

Osteoporosis is a disease affecting mainly women but also an increasing number of men. The destruction of the bone microarchitecture and the reduction of bone mass lead to increased fragility and pathologic bone fractures. Family studies and twin studies have shown that peak bone mass, mechanical strength, and physiological bone turnover are subject to genetic control. Vitamin D receptor polymorphisms were one of the first genetic factors suggested to influence bone phenotype, although their impact on bone metabolism was initially overestimated. Meanwhile, polymorphisms in numerous other genes such as collagen I alpha 1, estrogen receptor, transforming growth factor beta (TGF-beta), interleukin-1, interleukin-6, calcitonin, parathyroid hormone, and apolipoprotein E have been found to be associated with bone mineral density. In the interpretation of genetic findings, genetic differences between different ethnic groups, environmental factors such as calcium intake, vitamin D status, hormonal status, body size, and total body bone mineral density have to be considered. Understanding the molecular physiology of the genes described in this article and all genes influencing bone metabolism identified in the future will enable us to identify persons at risk for osteoporosis and to develop more specific therapies.
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PMID:[Genetics of osteoporosis]. 1151 78

The regulatory effects of the active form of vitamin D, 1-alpha, 25-dihydroxyvitamin D3 (1-alpha, 25 (OH)2D3) were assessed on the cytokine and chemokine secretion induced by sulfur mustard on human skin fibroblasts and human epidermal keratinocytes. Stimulation of human skin fibroblasts with sulfur mustard (10(-4) M for 24 hr at 37 degrees ) resulted in approximately a 5 times increase in the secretion of interleukin-6 and over a 10 times increase for interleukin-8, which was inhibited by 1-alpha, 25 (OH)2D3, at <or=10(-9) M. 1-alpha, 25 (OH)2D3 also suppressed interleukin-8 secretion by 5 times and interleukin-6 by 4 times on sulfur mustard-stimulated human epidermal keratinocytes at concentrations <or= 10(-9) M. The effect of 1-alpha, 25 (OH)2D3 was dose-dependent for the suppression of interleukin-6 and interleukin-8 induced by sulfur mustard on human skin fibroblasts/human epidermal keratinocytes, apparent at nanomolar concentrations. Our results indicate that the suppression of these inflammatory mediators by 1-alpha, 25 (OH)2D3 is dependent on the source of the primary cultures, cell densities, and kinetics of pretreatments. In contrast to the inhibition of cytokine/chemokine production, cell proliferation was enhanced by almost 1.7 times on treated human epidermal keratinocytes with 1-alpha, 25 (OH)2D3 (1 x 10(-9) M) after sulfur mustard-stimulation (10(-4) M for 24 hr at 37 degrees C). The observed enhancement diversified based on cell density, and kinetics of pretreatment with a maximal synergism (s) observed at 1 x 10(-9) M. Photomicrographs show typical signs of cellular degeneration caused by sulfur mustard such as chromatin condensation. The observed cellular degeneration was lessened when human epidermal keratinocytes were treated with 1-alpha, 25 (OH)2D3 (2 x 10(-9) M). 1-alpha, 25(OH)2D3 could be an alternative treatment for cutaneous inflammation disorders caused by sulfur mustard because we have demonstrated its ability to suppress inflammatory mediators and enhanced cell proliferation in human skin cells stimulated with sulfur mustard.
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PMID:Regulation of 1-alpha, 25-dihydroxyvitamin D3 on interleukin-6 and interleukin-8 induced by sulfur mustard (HD) on human skin cells. 1275 8

We investigated the capacity of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] to protect human keratinocytes against the hazardous effects of ultraviolet B (UVB)-irradiation, recognized as the most important etiological factor in the development of skin cancer. Cytoprotective effects of 1,25(OH)(2)D(3) on UVB-irradiated keratinocytes were seen morphologically and quantified using a colorimetric survival assay. Moreover, 1,25(OH)(2)D(3) suppressed UVB-induced apoptotic cell death. An ELISA, detecting DNA-fragmentation, demonstrated that pretreatment of keratinocytes with 1,25(OH)(2)D(3) 1 microM for 24 h reduced UVB-stimulated apoptosis by 55-70%. This suppression required pharmacological concentrations 1,25(OH)(2)D(3) and a preincubation period of several hours. In addition, 1,25(OH)(2)D(3) also inhibited mitochondrial cytochrome c release (90%), a hallmark event of UVB-induced apoptosis. Furthermore, we demonstrated that 1,25(OH)(2)D(3) reduced two important mediators of the UV-response, namely, c-Jun-NH(2)-terminal kinase (JNK) activation and interleukin-6 (IL-6) production. As shown by Western blotting, pretreatment of keratinocytes with 1,25(OH)(2)D(3) 1 microM diminished UVB-stimulated JNK activation with more than 30%. 1,25(OH)(2)D(3) treatment (1 microM) reduced UVB-induced IL-6 mRNA expression and secretion with 75-90%. Taken together, these findings suggest the existence of a photoprotective effect of active vitamin D(3) and create new perspectives for the pharmacological use of active vitamin D compounds in the prevention of UVB-induced skin damage and carcinogenesis.
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PMID:1,25-Dihydroxyvitamin D3 inhibits ultraviolet B-induced apoptosis, Jun kinase activation, and interleukin-6 production in primary human keratinocytes. 1285 33

Although neither calcium nor vitamin D has been shown to prevent osteoporosis in postmenopausal women alone, the combination does. Both calcium and vitamin D are commonly used in the treatment of osteoporosis. The estrogens and raloxifene both prevent bone loss in postmenopausal women, and the estrogens probably also decrease the risk of first fracture. There is good evidence that raloxifene prevents further fractures in postmenopausal women who have already had fractures and some evidence that estrogen does as well. Calcitonin increases bone mineral density in early postmenopausal women and men with idiopathic osteoporosis, and also reduces the risk of new fractures in osteoporotic women. The bisphosphonate alendronate prevents bone loss and reduces fractures in healthy and osteoporotic postmenopausal women, and in osteoporotic men. Risedronate is more potent and has fewer upper gastrointestinal side effects than alendronate, and reduces the incidence of fractures in osteoporotic women. Intermittent use of the potent bisphosphonate zoledronate also increases bone mineral density and may become an alternative in the prevention and treatment of osteoporosis. All of the agents discussed above prevent bone resorption, whereas teriparatide increases bone formation and is effective in the treatment of osteoporotic women and men. In the treatment of secondary osteoporosis associated with the use of glucocorticoids to treat inflammation or prevent rejection after transplantation, the bisphosphonates are effective. The agents that have undergone some clinical trialing as new or alternative drugs for the treatment of osteoporosis include tibolone, new SERMs, androgens, growth hormone, insulin-like growth factor-1 and stontium ranelate. The targets/drugs that are being developed to inhibit bone resorption include the OPG/ RANKL/RANK system, cathepsin K inhibitors, vitronectin receptor antagonists, estren, the interleukin-6 and gp130 system, cytokines and growth factors. New drugs/targets to promote bone formation include the commonly used lipid-lowering statins and the calcilytic release of PTH.
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PMID:Present and future pharmacotherapy for osteoporosis. 1456 85

In search of photoprotective agents, we recently demonstrated a protective effect of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] against different events mediated by ultraviolet B (UVB) in human keratinocytes. Pharmacological doses of 1,25(OH)(2)D(3) were required to obtain significant UVB protection; however, these doses cannot be used in vivo due to the calcemic properties of 1,25(OH)(2)D(3). Therefore, we evaluated the photoprotective capacities of two low-calcemic 14-epi analogues of 1,25(OH)(2)D(3), 19-nor-14-epi-23-yne-1,25(OH)(2)D(3) (TX 522) and 19-nor-14,20-bisepi-23-yne-1,25(OH)(2)D(3) (TX 527). Using cultured human keratinocytes, we investigated the influence of TX 522 and TX 527 on two hallmark events in UVB-irradiated keratinocytes: the induction of apoptosis and the production of interleukin-6 (IL-6). Treatment of the keratinocytes with TX 522 or TX 527, 24 h before irradiation, resulted in a significant and dose-dependent reduction of both UVB-induced apoptosis and IL-6 production. Both analogues were equally efficient in their anti-UVB effects and at least 100 times more potent than 1,25(OH)(2)D(3). We further demonstrated that metallothionein (MT) mRNA expression was clearly induced by 1,25(OH)(2)D(3) and both analogues. MT acts as a radical scavenger in oxygen-mediated UVB injury and its induction may therefore be relevant for the anti-UVB effects of 1,25(OH)(2)D(3) and both analogues. Taken together, these findings create new perspectives for the use of active vitamin D analogues as photoprotective agents.
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PMID:Two 14-epi analogues of 1,25-dihydroxyvitamin D3 protect human keratinocytes against the effects of UVB. 1504 83

Rheumatoid Arthritis (RA) is a chronic inflammatory disease resulting in diarthrodial joints inflammation (particularly joints of hands, wrists, feet, knees, cubitus, ankles, shoulder, etc.) that is manifested by swelling and functional impairment. The associated complications, osteoporosis and cardiovascular disease, make RA important in public health terms. During the active phase of disease, elevated plasma concentrations of inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNF-alpha) and acute-phase proteins, lead to reduction of fat free body mass (FFM) with a loss mean of 15% of cell body mass (CM) and consequent reduction of muscle strength. The pharmacological therapy (non steroidal anti inflammatory drugs (NSAIDs), slow acting antirheumatic drugs and corticosteroids), have the potential to cause side-effects, such as gastrointestinal bleeding, bone loss beyond to increase the requirement of some nutrients and reduce their absorption. The diet may play role in the management of RA, particularly in alleviating the symptoms of the disease, combating the side-effects of therapy and reducing the risk of complications. The increase of the caloric and proteic intake is not sufficient to offset a increased metabolic rhythm and important proteic catabolism but a diet balanced may warrant an adequate intake of nutrients. The carbohydrates of the diet provide 55-60% of the caloric intake, the diet is normo-proteinic or hyper-proteinic in the active phase of disease, and lipids represent 25-30% of the caloric intake (saturated, monounsaturated, polyunsaturated fatty acids in the ratio 1:1:1). omega-3 fatty acids supplementation, in combination with reduction of fatty acids omega-6 and adequate intake of monounsaturated fatty acids induce improvement in symptoms and sometimes a reduction in NSAIDs usage. Proper antioxidant nutrients (Vitamin A, Vitamin C, selenium) may provide an important defence against the increased oxidant stress and a supplementation of folate and vitamin B12, in patients treated with methotrexate (MTX), reduce the incidence of side effects and offset the elevation in plasma homocysteine frequent in these patients. Calcium and vitamin D, in patients treated with corticosteroids, reduce the bone loss, while a supplementation with iron may prevent anaemia. Finally, elimination diets may be feasible therapy only in patients with positive skin prick test.
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PMID:[Diet, nutrition and rheumatoid arthritis]. 1604 32

Reciprocal interactions between tumor cells and endothelial cells constitute the most important stage of tumor metastasis. There is growing evidence suggesting that beta-estradiol and vitamin D modulate the progression of steroid-sensitive breast cancers. In keeping with those results, the purpose of the study reported here was to determine the cytotoxic and antiproliferative activity of tamoxifen (TAM) in the T47D human breast cancer cell line depending on the cell culture model (three-dimensional (3D, spheroid) or two-dimensional (2D, monolayer)) and to estimate the antiproliferative activity of vitamin D in balanced TAM/beta-estradiol conditions. The study was also designed to investigate whether vitamin D might influence interleukin-6 (IL-6) and metalloproteinase-2 (MMP-2) production in a co-culture of T47D cell spheroids with an endothelial cell monolayer in the presence of beta-estradiol and TAM. Spectrophotometric analysis with MTT revealed that the cytotoxic and antiproliferative activity of TAM was dependent on the culture model, the density of cell culture, and culture medium supplements. In balanced TAM/beta-estradiol medium, vitamin D only slightly inhibited T47D cell proliferation in both 2D and 3D cultures. Direct contact of tumor cell spheroids with the endothelium induced production of MMP-2 and IL-6, which was significantly inhibited in TAM/beta-estradiol balanced medium. Addition of vitamin D further inhibited MMP-2 production, but enhanced the production of IL-6 as was shown by ELISA assay. Our co-culture model in TAM/beta-estradiol balanced medium proved to be useful for examining direct and paracrine interactions of tumor cells with the endothelium in conditions that were closer to in vivo conditions than in the standard 2D model.
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PMID:Vitamin D, tamoxifen and beta-estradiol modulate breast cancer cell growth and interleukin-6 and metalloproteinase-2 production in three-dimensional co-cultures of tumor cell spheroids with endothelium. 1632 60


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