UNIPROT:P05231 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

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

Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) are candidate cytokines which are produced by osteoblastic linage cells and promote osteoblast apoptosis, osteoclastogenesis and bone resorption. Here, we examined the effect of (+)-catechin, one of the most common grape flavonols, on osteoblastic MC3T3-E1 cells. (+)-Catechin caused a significant elevation of cell survival at 10(-5) and 10(-4) M and alkaline phosphatase activity at 10(-5) M. Also, treatment with (+)-catechin (10(-5) M) decreased bone-resorbing cytokines (TNF-alpha and IL-6) production and apoptosis in osteoblasts. Our data indicate that the reduction of bone-resorbing cytokines and apoptosis in osteoblasts by (+)-catechin may result in the prevention and therapy for osteoporosis and inflammatory bone diseases.
...
PMID:Effects of (+)-catechin on the function of osteoblastic cells. 1267 36

Recently, a G/C polymorphism was found at position -573 of the interleukin-6 ( IL-6) gene promoter. We investigated how this genetic polymorphism relates to IL-6 production and osteoporosis in elderly Japanese women. Genomic DNA was extracted from an aliquot of monocytes in the bone marrow; the monocytes were simultaneously used to form osteoclast-like multinucleated cells (MNCs) and to produce IL-6. Of the 47 subjects with fractures, 96% had a C allele at position -573 of the IL-6 gene. Only 2 subjects possessed homozygotes of G at that position. We investigated IL-6 levels, MNC formation in bone marrow culture, and femoral neck bone mineral density (BMD) in the subjects with the GC and CC genotypes. There were no significant differences between these genotypes as regards IL-6 levels, MNC formation, and femoral neck BMD. However, in the CC genotype, there was a negative relationship between femoral neck BMD and IL-6 levels, and between femoral neck BMD and MNC formation, whereas in the GC genotype and combined (GC + CC) genotypes, femoral neck BMD tended to be related to IL-6 levels and MNC formation. Moreover, the stromal cells in the CC genotype showed higher IL-1alpha-stimulated IL-6 production than did the stromal cells in the GC genotype. Our findings suggest that important information might be obtained not only by continued comparison of different genotypes but also by comparative study within each particular genotype.
...
PMID:Association between bone loss and promoter polymorphism in the IL-6 gene in elderly Japanese women with hip fracture. 1281 27

Osteopenia and osteoporosis have recently been described as complications of antiretroviral therapy in HIV-infected patients. The advent of highly active antiretroviral therapy in conjunction with improved standard antiviral and antibiotic regimens has dramatically changed the clinical course of HIV infection, resulting in prolonged survival. The pathogenesis and role of each individual medication are poorly understood. Avascular necrosis has also been described in AIDS patients receiving or not receiving antiretroviral therapy. This article is a clinically focused review of the literature on osteopenia, osteoporosis, and mineral metabolism related to HIV infection. In patients with HIV infection, the risks of osteopenia and osteoporosis are not very clear. The suggested risk factors for the development of osteopenia are use of protease inhibitors, longer duration of HIV infection, high viral load, high lactate levels, low bicarbonate levels, raised alkaline phosphatase level, and lower body weight before antiretroviral therapy. There have also been a few case reports of pathologic fractures in AIDS patients with antiretroviral therapy-induced osteopenia and osteoporosis. The underlying mechanism triggering bone loss in HIV-infected patients is unknown. The proinflammatory cytokines tumor necrosis factor and interleukin-6 have been found to be constitutionally produced in increased amounts in HIV-positive individuals, and they may have a role in osteoclast activation and resorption. Serum markers of bone formation are decreased and resorption is increased in patients with advanced clinical disease. Hypocalcemia, hypercalcemia, and abnormalities of the parathyroid hormone axis have been described in HIV infection. Histomorphometric analyses have shown altered bone remodeling in HIV-infected patients when compared with controls. Patients with known risk factors for osteoporosis-advancing age, low body weight, and prolonged duration of HIV infection-and those receiving protease inhibitor treatment should be considered for dual x-ray absorptiometry imaging. If bone mineral density is osteopenic or osteoporotic, then the patient should also be screened for other known medical causes of osteoporosis and consider treatment with a bisphosphonate or, if hypogonadal, testosterone replacement under close monitoring.
...
PMID:HIV infection--a risk factor for osteoporosis. 1284 38

In order to observe the expression and cellular localization of interleukin-6 (IL-6) mRNA in bone tissue, ovaries of the rats were excised to develop osteoporosis model. The expression of IL-6 mRNA in bone tissues was detected by using dot blot hybridization assay and the cells producing IL-6 identified and localized by using in situ hybridization respectively. The results showed that the expression of IL-6 mRNA was significantly increased in the ovariectomized rats as compared with that in normal control rats and strong IL-6 mRNA hybridization signals were detected in lining cells, osteoblasts and osteocytes. It was suggested that loss of ovarian function induced in vivo osteoblast lineage increased IL-6 mRNA expression. IL-6 might play important roles in the development of bone loss following ovariectomy.
...
PMID:Expression and cellular localization of interleukin-6 mRNA in ovariectomized rats. 1284 32

Bone metabolism requires tightly coupled activities exhibited by two unique cell populations, the bone-resorbing osteoclasts and the bone-forming osteoblasts. Imbalance in the function of these two cell types can result in osteoporosis, a condition characterized by loss in bone integrity and of bone mass. We developed a human bone cell culture model that allows the in vitro study of bone formation and osteoclastogenesis and employed this bone model for the screening and pharmacological analyses of protein and small molecule therapeutics. The cytokines, interleukin-6 (IL-6) and granulocyte macrophage colony stimulating factor (GM-CSF), play an intricate role in osteoclastogenesis in this system. Neutralizing antibodies to IL-6 and GM-CSF decreased the formation of osteoclast-like cells. SP500263, an early lead compound from a novel class of selective estrogen receptor modulators (SERMs), was more efficacious than estrogen and comparable to raloxifene in blocking cytokine production and formation of osteoclast-like cells. Our research demonstrates the usefulness of the in vitro co-culture model in the dissection of molecular events relevant to bone metabolism and provides greater insight into a potential novel role for cytokines in bone resorption. Furthermore, representatives of the SP500263 family of SERMs may be effective as therapeutics for the treatment of osteoporosis.
...
PMID:SP500263, a novel SERM, blocks osteoclastogenesis in a human bone cell model: role of IL-6 and GM-CSF. 1290 49

Osteoporosis is a disease characterized by low bone mineral density (BMD) and poor bone quality. Peak bone density is achieved by the third decade of life, after which bone is maintained by a balanced cycle of bone resorption and synthesis. Age-related bone loss occurs as the bone resorption phase outweighs the bone synthesis phase of bone metabolism. Heritability accounts for up to 90% of the variability in BMD. Chromosomal loci including 1p36, 2p22-25, 11q12-13, parathyroid hormone receptor type 1 (PTHR1), interleukin-6 (IL-6), interleukin 1 alpha (IL-1alpha) and type II collagen A1/vitamin D receptor (COL11A1/VDR) have been linked or shown suggestive linkage with BMD in other populations. To determine whether these loci predispose to low BMD in the Irish population, we investigated 24 microsatellite markers at 7 chromosomal loci by linkage studies in 175 Irish families of probands with primary low BMD (T-score < or = -1.5). Nonparametric analysis was performed using the maximum likelihood variance estimation and traditional Haseman-Elston tests on the Mapmaker/Sibs program. Suggestive evidence of linkage was observed with lumbar spine BMD at 2p22-25 (maximum LOD score 2.76) and 11q12-13 (MLS 2.55). One region, 1p36, approached suggestive linkage with femoral neck BMD (MLS 2.17). In addition, seven markers achieved LOD scores >1.0, D2S149, D11S1313, D11S987, D11S1314 including those encompassing the PTHR1 (D3S3559, D3S1289) for lumbar spine BMD and D2S149 for femoral neck BMD. Our data suggest that genes within a these chromosomal regions are contributing to a predisposition to low BMD in the Irish population.
...
PMID:Suggestive linkage of 2p22-25 and 11q12-13 with low bone mineral density at the lumbar spine in the Irish population. 1456 92

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.
...
PMID:Present and future pharmacotherapy for osteoporosis. 1456 85

Osteoporosis is characterized by a decrease in bone mass as well as a deterioration of the bone architecture resulting in an increased risk of fracture. The disease is multifactorial, and it depends on environmental and genetic factors. Twin studies have shown that genetic factors account for 60-80% of the variance in bone mineral density, the best predictor of the risk of osteoporosis. There are different approaches to identify these genetic factors. Linkage studies in human and experimental animals have defined multiple loci that regulate bone mass but most of the genes responsible for this effect remain to be defined. The 11q12-13 locus was the first that was linked to bone mineral density of the young female and special bone diseases like high bone mass syndrome and osteoporosis-pseudoglioma syndrome. Both diseases appear to be in association with LDL receptor-related protein 5 gene mutation. The effect of LDL receptor-related protein 5 on bone metabolism had not been known only genetic methods suggested it. The effect of LRP5 in osteoporosis pathogenesis requires more investigation. Association and linkage studies have been performed in order to identify candidate genes in the pathogenesis of osteoporosis. Vitamin D receptor gene was the first candidate, however its effect is controversial. Other candidates, such as insulin like growth factor, interleukin-6, estrogen receptor alpha, transforming growth factor beta show no or small effect on bone mineral density or fracture frequency. To date only Sp1 polymorphism of collagen gene seems to have a consistent effect on bone fragility. The improved understanding of osteoporosis genetics should lead to better diagnosis of this disease and new treatment and prevention strategies.
...
PMID:[Genetic background of osteoporosis]. 1456 76

The ability of parathyroid hormone (PTH) to enhance bone formation has recently been exploited in the treatment of osteoporosis. However, the underlying mechanisms are unknown. Osteoblasts, the bone-forming cells, derive from multipotential bone marrow stromal precursors called colony-forming units-fibroblastic (CFU-F) upon culture ex vivo. Adhesion of such stromal precursors to bone is likely to be an early event in the anabolic response of bone to PTH. To test this, we measured the number of CFU-F that could be extracted from murine bone marrow after administration of an anabolic dose of PTH. We found that a very early response is a dramatic reduction, starting within 2 h, in the number of CFU-F that could be extracted from their bone marrow. We then tested whether PTH has the ability to activate adhesion of CFU-F in vitro. For this, bone marrow cells were incubated in PTH for varying times. Non-adherent cells were then removed, and the adherent cells were incubated in PTH-free medium for 14 days to assess, as colony formation, the number of CFU-F that had adhered in the preceding period. We found that incubation in PTH caused a substantial increase in the number of CFU-F that adhered within 24 h. This increase was abrogated by peptidic inhibitors of integrins. The increase did not seem to be mediated through a PTH-induced increase in interleukin-6, since interleukin-6 had no effect on CFU-F numbers when substituted for PTH. Similarly, adhesion was unaffected by incubation of bone marrow cells in dibutyryl cyclic AMP, nor by inhibitors or donors of nitric oxide. However, activation of CFU-F in vitro by PTH was strongly inhibited by indomethacin and mimicked by prostaglandin E(2), and indomethacin reversed the PTH-mediated reduction of CFU-F that could be extracted from mouse bone marrow. These results suggested that PTH rapidly activates adhesion of CFU-F to plastic or bone surfaces. This activation may represent an early event in the anabolic response of bone cells to PTH.
...
PMID:Parathyroid hormone activates adhesion in bone marrow stromal precursor cells. 1501 5

In this prospective study, we aimed to evaluate the effect of simvastatin on bone metabolism and the correlation between changes in bone turnover parameters and serum cytokine levels. For this purpose, 38 postmenopausal subjects with hypercholesterolemia (>240 mg/dl), not on osteoporosis treatment, were studied. Simvastatin was started at a dose of 20 mg daily and continued for 3 months. Six patients were excluded from the study during the follow-up period. Pre- and post-treatment samples were analyzed for bone alkaline phosphatase (BAP) and osteocalcin (OCL), as markers of bone formation; for carboxyterminal telopeptide of collagen I (CTX), as a marker of bone resorption; and for interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) cytokine levels. Total cholesterol level was decreased from 262.1 +/- 30.9 to 210.2 +/- 35.6 mg/dl after simvastatin treatment (P < 0.0001). While no significant change was observed in serum CTX level, BAP and OCL levels were significantly increased (from 120.8 +/- 56.6 to 149.5 +/- 57.6 IU/l [P = 0.008], and from 20.8 +/- 12.6 to 34.7 +/- 18.4 microg/l [P = 0.015], respectively). In the analysis of cytokines, while no significant change was observed in IL-6 levels, the TNF-alpha level was found to be significantly decreased after simvastatin treatment (from 77.9 +/- 31.6 pg/ml to 23.5 +/- 12.6 pg/ml [P = 0.021]). Individual changes in TNF-alpha levels showed a moderate negative correlation with the individual changes in BAP and OCL levels (r = -0.550 [P = 0.001], and r = -0.497 [P = 0.004], respectively). In conclusion; 20-mg daily simvastatin treatment for 3 months significantly increased BAP and OCL levels (markers of bone formation) in hypercholesterolemic postmenopausal subjects, without affecting bone resorption. These findings support the idea that simvastatin has an anabolic effect on bone formation. Additionally, the presence of a negative correlation between TNF-alpha levels and the anabolic bone parameters suggests that a cytokine-lowering effect of simvastatin may also be involved in the remodeling process and could exert some additive beneficial effect on bone metabolism.
...
PMID:The effect of simvastatin on serum cytokine levels and bone metabolism in postmenopausal subjects: negative correlation between TNF-alpha and anabolic bone parameters. 1522 96

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>