UNIPROT:P05231 - FACTA Search

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

Genetic factors play an important role in the pathogenesis of several bone diseases. The the most important of these is osteoporosis-a common condition characterised by reduced bone mass and increased fracture risk, which affects up to 40% of women and 12% of men at some point during life. Twin and family studies suggest that up to 85% of the variance in bone mineral density is genetically determined. Clinical studies have identified several candidate genes which may be involved in this process. The vitamin D receptor gene (VDR) has been most widely studied, but the relationship between polymorphisms of the VDR and bone density has been found to be inconsistent and poorly reproducible in different populations. Polymorphisms in and around the genes encoding interleukin-6, tumour necrosis factor beta and the oestrogen receptor have also been associated with bone mass in some populations, but these have not been widely studied. In contrast, a functional polymorphism has been identified at a binding site for the transcription factor Sp1 in the collagen type I alpha I gene, which is associated with bone mass and osteoporotic fracture in several populations, suggesting that genotyping at this site may be of potential clinical value in the assessment of fracture risk. The importance of genetic factors in the regulation of bone mass, coupled with the ability to test for candidate polymorphisms in genomic DNA, indicates that genetic testing may play a role in the future assessment of osteoporotic fracture risk. The clinical value of this approach is at present unclear, but is likely to be an important area for future development as new polymorphisms are identified by genome wide searches and further analysis of candidate genes.
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PMID:Genetic markers of bone metabolism and bone disease. 912 77

The release of metals from total joint prostheses may contribute to periprosthetic bone loss manifested as osteolysis. The effects of titanium, cobalt, and chromium on human osteogenic sarcoma cells (osteoblastlike cells) were investigated in vitro. Titanium, cobalt, and chromium at concentrations of 1, 10, and 100 ng/ml did not cause any changes in the cell growth, viability, and injury after 72-hour incubation with the cells. Titanium, cobalt, and chromium at concentrations ranging from 0.01 to 100 ng/ml significantly enhanced the release of interleukin-1 beta and tumor necrosis factor-alpha by lipopolysaccharide stimulated human osteogenic sarcoma cells, whereas they did not alter the release of transforming growth factor-beta 1. Cobalt at concentrations ranging from 0.1 to 100 ng/ml significantly enhanced the release of interleukin-6, but titanium and chromium did not. Cobalt and chromium at concentrations of 10 and 100 ng/ml significantly inhibited the release of osteocalcin by human osteogenic sarcoma cells, whereas titanium had no effect. Titanium, cobalt, and chromium at concentrations of 10 and 100 ng/ml significantly inhibited the synthesis of Type I collagen by human osteogenic sarcoma cells. Cobalt and chromium inhibited the cell proliferation in response to lipopolysaccharide stimulation, whereas titanium did not. The data presented in this article suggest that the metal induced disregulation of cytokine release and osteoblast dysfunction may play an important role in the induction of osteolysis in patients with total joint arthroplasties.
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PMID:Prosthetic metals interfere with the functions of human osteoblast cells in vitro. 918 23

In order to investigate the role of neural regulation in corneal epithelial healing, we examined the effect of substance P (SP) on corneal epithelial migration using an organ culture system of rabbit corneas. We investigated the synergistic effects of SP with (1) growth factors: epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and transforming growth factor-beta(TGF-beta); (2) extracellular matrix proteins: fibronectin, vitronectin, laminin, and collagen type IV; and (3) cytokines: interleukin-1alpha (IL-1alpha), IL-1beta, and interleukin-6 (IL-6). Rabbit corneal blocks were cultured in the absence or presence of various reagents for 24 hr. The corneal blocks were then fixed, dehydrated, embedded in paraffin and stained by hematoxylin-eosin, and the length of the path of epithelial migration was measured. The addition of SP alone, at concentrations up to 50 microg ml-1, did not affect epithelial migration. EGF, fibronectin, vitronectin, collagen type IV, and IL-6 stimulated epithelial migration, but bFGF, TGF-beta, laminin, IL-1alpha, and IL-1betadid not. The stimulatory effect of EGF on the epithelial migration was enhanced by the presence of SP. This synergistic effect of SP and EGF on corneal epithelial migration was abolished by the addition of an SP antagonist or enkephalinase. Other neurotransmitters (vasoactive intestinal peptide, calcitonin gene-related peptide, acetylcholine chloride, norepinephrine, serotonin) and tachykinins (neurokinin A, neurokinin B, kassinin, eledoisin, physalaemin) were examined, but none exhibited a synergistic effect with EGF. Interestingly, EGF alone stimulated the incorporation of 3H-thymidine into corneal epithelial cells, but the addition of SP with EGF did not enhance this effect. These results demonstrate that SP enhanced the EGF stimulation of corneal epithelial migration in vitro in a specific manner, suggesting a possible role of SP as a modulator of epithelial wound healing.
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PMID:Synergistic effect of substance P with epidermal growth factor on epithelial migration in rabbit cornea. 929 69

Lung epithelial cells (A549) synthesize and secrete fibrinogen (FBG) in vitro when stimulated with interleukin-6 and dexamethasone. This FBG secretion is polarized in the basolateral direction, suggesting that FBG is a component of the extracellular matrix (ECM). Immunofluorescent staining of A549 cells showed a fibrillar pattern of FBG, similar to the staining detected using antibodies against the matrix constituents, collagen type IV and fibronectin (FN). The same pattern of staining was detected using antibodies against fibrinopeptides A and B, as well as with the T2G1 monoclonal antibody against the fibrin-specific epitope, beta15-21. Matrix staining was unaltered in the presence of the thrombin inhibitor, hirudin, or the plasmin inhibitor, aprotinin, consistent with the interpretation that matrix deposition of FBG does not require such enzymatic action. Metabolic labeling studies confirmed that FBG secreted from A549 cells or deposited into the ECM showed no evidence of thrombin or plasmin proteolytic processing or of transglutaminase-mediated covalent cross-linking (gamma-gamma dimers or alpha-polymers). Incubation of either A549 cell-derived or purified plasma FBG with cultures of human foreskin fibroblasts resulted in FBG deposition in the ECM that colocalized with matrix fibrils containing endogenously produced FN and laminin (LN). Binding of FBG to this exogenously produced matrix was unaltered by inhibition of thrombin and plasmin action, yet also exhibited exposure of the fibrin-specific epitope, beta15-21. The majority (approximately 70%) of newly synthesized and secreted FBG is bound to the cell surface as determined by its trypsin-sensitivity. Cell surface-bound FBG is initially deoxycholate-soluble, which, over time, becomes incorporated in the deoxycholate-insoluble ECM in a similar fashion to FN. These data suggest that matrix incorporation requires the binding of secreted FBG to cell-associated matrix assembly sites. However, unlike FN, FBG in the ECM is composed of the dimeric protamer (A alpha/B beta/gamma gamma) and not high molecular weight polymers indicative of fibrin. This study provides evidence that deposition of FBG in both endogenous and exogenously produced matrices results in conformational changes that occur independently of thrombin cleavage. This matrix-bound FBG, on which unique cell-reactive domains are likely exposed, could augment cellular response mechanisms evoked during injury and inflammation.
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PMID:Thrombin cleavage-independent deposition of fibrinogen in extracellular matrices. 932 31

Recent studies have revealed the potential importance of the extracellular matrix (ECM) in the modulation of mesangial cell (MC) function. Interleukin-6 (IL-6) is produced by MCs and was shown to induce MC proliferation, acting as an autocrine growth factor. Heparin is a known inhibitor of MC proliferation. It was shown to modulate ECM synthesis by cultured MCs. The action of heparin on IL-6 synthesis by MCs is presently unknown. We investigated the effect of heparin on IL-6 production when MCs were cultured with or without type-IV collagen, a major constituent of ECM. When MCs were cultured without coating, heparin significantly decreased their IL-6 production; on type-IV collagen, heparin had no significant effect. When tumor necrosis factor alpha (TNF-alpha) was used to stimulate the cells to produce IL-6, heparin was able to decrease the stimulatory effect of TNF-alpha when the cells were cultured on plastic but not when in contact with type-IV collagen. Thus we conclude that heparin has an inhibitory effect on IL-6 secretion by MCs that is prevented by type-IV collagen.
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PMID:Influence of heparin and type-IV collagen on IL-6 synthesis by rat glomerular mesangial cells. 934 90

Interleukin-6 (IL-6) produced by osteoblastic cells plays an important role in the regulation of bone remodeling, mainly by stimulating osteoclast action. Although the IL-6 receptor is also found in osteoblastic cells, whether IL-6 exerts autocrine effects on osteoblastic cells is a matter of debate. This led us to study the effects of IL-6 on proliferation, osteoblastic activity as well as mRNA expression of various osteoblastic proteins in human bone marrow stromal osteoprogenitor cells (hBMSC). IL-6 did not affect cell proliferation assessed by [3H]-thymidine incorporation and osteoblastic activity determined by alkaline phosphatase activity and 45Ca incorporation. The expression of mRNAs for alkaline phosphatase, alpha 1 (I)-collagen, osteopontin and decorin also did not change significantly by IL-6 treatment. These results show that IL-6 does not have a significant autocrine role in regard to proliferation and osteoblastic activity of hBMSC.
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PMID:Lack of autocrine effects of IL-6 on human bone marrow stromal osteoprogenitor cells. 937 5

Interleukin-6 (IL-6) is overproduced in the joints of patients with rheumatoid arthritis (RA) and, based on its multiple stimulatory effects on cells of the immune system and on vascular endothelia, osteoclasts, and synovial fibroblasts, is believed to participate in the development and clinical manifestations of this disease. In this study we have analysed the effect of ablating cytokine production in two mouse models of arthritis: collagen-induced arthritis (CIA) in DBA/1J mice and the inflammatory polyarthritis of tumor necrosis factor alpha (TNF-alpha) transgenic mice. IL-6 was ablated by intercrossing an IL-6 null mutation into both arthritis-susceptible genetic backgrounds and disease development was monitored by measuring clinical, histological, and biochemical parameters. Two opposite responses were observed; while arthritis in TNF-alpha transgenic mice was not affected by inactivation of the IL-6 gene, DBA/1J, IL-6(-/-) mice were completely protected from CIA, accompanied by a reduced antibody response to type II collagen and the absence of inflammatory cells and tissue damage in knee joints. These results are discussed in the light of the present knowledge of cytokine networks in chronic inflammatory disorders and suggest that IL-6 receptor antagonists might be beneficial for the treatment of RA.
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PMID:Interleukin 6 is required for the development of collagen-induced arthritis. 946 96

The effects of a polymethylmetacrylate (PMMA) powder with a diameter between 0.5 and 25 mu m have been studied in vitro on several human osteoblast populations obtained from different sources. Parameters of cell activity such as cell growth, collagen synthesis, osteocalcin, and interleukin-6 (IL-6) production have been evaluated. Cell proliferation and collagen synthesis were inhibited after exposure to bone cement, whereas osteocalcin and IL-6 production were stimulated. These results suggest that PMMA particles could affect osteoblast activity in a way that could contribute, together with other factors, to periprosthetic osteolysis through two different pathways: a reduced periprosthetic bone formation due to the reduced osteoblast proliferation and collagen synthesis, and an osteoblast-mediated activation of osteoclastic bone resorption as suggested by the increased osteocalcin and IL-6 synthesis. In fact, osteocalcin has been demonstrated to have a role in osteoclast recruitment to bone surfaces, and IL-6 is known to induce osteoclastogenesis and to directly stimulate bone resorption.
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PMID:Response of human osteoblasts to polymethylmetacrylate In vitro. 950 63

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

Chronic sinusitis in allergic (ACS) and nonallergic (NCS) patients is characterized by persistent inflammation and subepithelial fibrosis of the sinus mucosa. The inflammatory infiltrate is rich in T lymphocytes, monocyte/macrophages, plasma cells, and eosinophils. Th2-type cytokines are thought to regulate inflammatory cell recruitment, activation, survival, and the release of tissue-damaging mediators. Interleukin-6 is a proinflammatory Th2-type cytokine that stimulates fibroblast proliferation and collagen synthesis. Expression of interleukin-6 has been reported in pulmonary fibrosis and a number of other conditions associated with fibrotic tissue changes. In vitro studies have indicated that interleukin-6 is produced by macrophages, T cells, eosinophils, mast cells, and other cell types. Here we examined interleukin-6 messenger RNA and immunoreactivity in the sinus epithelium and subepithelium of subjects with ACS and NCS by in situ hybridization and immunocytochemistry, performed on sinus biopsy and polyp sections obtained from patients. Nasal turbinate biopsy specimens from normal volunteers were used as controls. Interleukin-6 messenger RNA and immunoreactivity were expressed by a significantly greater proportion of epithelial and subepithelial cells in ACS and NCS subjects than in normal controls. There was no difference in epithelial or subepithelial interleukin-6 expression between ACS and NCS patients. Colocalization studies revealed that macrophages, T cells, eosinophils, and mast cells are sources of interleukin-6 messenger RNA in ACS and NCS. The numbers of interleukin-6 messenger RNA-positive cells coexpressing immunoreactivity for the mast-cell marker were significantly greater in ACS than in NCS subjects. The results of this study suggest a role for interleukin-6 in the inflammatory response of chronic sinusitis.
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PMID:Interleukin-6 expression in chronic sinusitis: colocalization of gene transcripts to eosinophils, macrophages, T lymphocytes, and mast cells. 956 Jan 3

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