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

1. We studied the changes in interleukin-1 and interleukin-6 secretion by peripheral blood mononuclear cells from 12 premenopausal women after oophorectomy and seven premenopausal women who had undergone simple hysterectomy. 2. The results showed that 1 month after surgery interleukin-1 secretion increased by 414 +/- 171% (mean +/- SEM) and interleukin-6 secretion increased by 1354 +/- 481% in oophorectomized women, whereas only non-significant fluctuations in the secretion of both cytokines (-9% +/- 29% for interleukin-1 and -31% +/- 19% for interleukin-6) were seen in the women who had undergone simple hysterectomy. The difference between the two groups was significant (P = 0.035 for interleukin-1 and P = 0.003 for interleukin-6). In addition, oophorectomy, but not simple hysterectomy, was followed by significant increases in plasma ionized calcium concentration (P < 0.05), plasma alkaline phosphatase activity (P < 0.01) and plasma osteocalcin concentration (P < 0.02), and a reduction in plasma parathyroid hormone level (P < 0.01). 3. We conclude that ovary ablation may modify cytokine secretion by peripheral blood mononuclear cells. If this phenomenon occurs in the bone microenvironment, it could be important in the loss of bone observed after oophorectomy. However, the possibility of an independent alteration induced by the lack of gonadal hormones but unrelated to bone turnover cannot be excluded.
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PMID:Spontaneous release of interleukin-I and interleukin-6 by peripheral blood mononuclear cells after oophorectomy. 133 Apr 14

By interacting with a structurally identical receptor, parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) display a common spectrum of action on the transport of mineral elements in bone and kidney. In vivo, PTH/PTHrP similarly reduce the renal tubular reabsorption of inorganic phosphate (Pi) and increase that of calcium. The hypercalcemic effect of PTHrP is due to an increase in both bone resorption and renal calcium reabsorption, the latter through a sodium-independent mechanism. The PTHrP-stimulated bone resorption can be totally inhibited by bisphosphonate therapy. Despite that, the fall in calcemia is moderate, indicating that the PTHrP main hypercalcemic action is due to the stimulation of the renal transport of calcium. For identical effects on renal ionic transports, PTHrP appears to less stimulate bone formation than PTH. These experimental findings are similar to clinical observations in patients with primary hyperparathyroidism or with solid malignant tumors. In vitro, the effects of PTH(1-34), PTHrP(1-34) and PTHrP(1-141) on cAMP production and sodium-dependent phosphate transport (NaPiT) are similar in kidney cells, where NaPiT is specifically inhibited by either peptide. This effect is attenuated by the competitive inhibitor [D-Trp12,Tyr34]bPTH(7-34)amide. Transforming growth factor-alpha similarly modulates the cAMP and NaPiT responses to PTH/PTHrP. In cultured mammary cells isolated from lactating rats, PTHrP elicits a 2-fold increase of cAMP production. Various products of bone and stromal cells, and of leukocytes, such as Interleukin-6 or Tumor necrosis factor-alpha, as well as high extracellular calcium concentration enhance PTHrP production by cultured lung squamous cell carcinoma and Leydig tumor cells, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Actions of parathyroid hormone and parathyroid hormone-related protein. 133 36

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

Recombinant human interleukin-6 (IL-6) was assessed for its ability to stimulate bone resorption in prelabeled mouse calvariae in vitro. IL-6 had no effect on bone resorption at concentrations ranging from 300 to 10,000 U/ml (3-1000 pg/ml). Neither the presence of indomethacin nor prolonged incubation periods (96 h) affected this result. IL-6 did not affect resorption stimulated by human recombinant IL-1 alpha (rIL-1 alpha) but inhibited resorption stimulated by parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. rIL-1 alpha, PTH, and 1,25-(OH)2D3 induced IL-6 release by calvariae. We conclude from these studies that IL-6 does not stimulate bone resorption in neonatal mouse calvariae. However, it may act as a locally produced inhibitor and therefore a paracrine regulator of bone resorption induced by osteotropic hormones. IL-6 could also function as a long-range stimulator of systemic reactions and acute-phase responses to local inflammatory and neoplastic lesions in bone.
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PMID:Interleukin-6 does not stimulate bone resorption in neonatal mouse calvariae. 179 61

Interleukin-6 (IL-6) is a cellular regulatory molecule, the diverse functions of which relate to cells both within and outside the immune system. In this report we demonstrated that bone tissue, specifically osteoblasts, produce interleukin-6 and that this function can be modulated by the osteotrophic hormone parathyroid hormone (PTH). Given that the complex process of bone remodeling is now thought to be regulated not only by systemic hormones but also by locally produced factors, the existence of a parathyroid hormone-stimulated production of interleukin-6 by osteoblasts may have important physiological significance.
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PMID:Interleukin-6 is produced by bone and modulated by parathyroid hormone. 281 8

A state of severe bone loss is often observed in patients and animals suffering from phosphate (Pi) depletion. Conversely, Pi surfeit may have an anabolic effect on bone and may antagonize bone resorption. To study whether Pi has a direct effect on the production of the bone-resorbing interleukin-6 (IL-6) by osteoblasts, we cultured MC3T3-E1, UMR-106, and isolated rat calvaria cells in media containing varying concentrations of Pi (0-3 mM) and measured the production of IL-6 released into the media. IL-6 production was steady with time and was stimulated by parathyroid hormone, 1,25-dihydroxyvitamin D3, and interleukin-1 alpha. However, IL-6 production did not change with varying Pi concentrations. We concluded that the IL-6 production by osteoblastic cells is independent of the medium Pi.
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PMID:Production of interleukin-6 by osteoblastic cells is independent of medium inorganic phosphate. 758 75

Endothelins are a class of peptides that are produced by and elicit responses in many tissues. A growing literature documents the presence and effects of endothelins in bone. Both endothelinA and endothelinB receptors have been demonstrated in osteoblastic cells by ligand binding. Major signal transduction pathways for endothelin in bone cells appear to be stimulation of phospholipid turnover, by activation of A, C and D phospholipases, stimulation of calcium flux from intracellular and extracellular stores and activation of tyrosine kinases. Endothelins also modulate calcium signaling elicited by other agents in osteoblastic cells. The parathyroid hormone-stimulated calcium transient in UMR-106 cells is enhanced by endothelins, acting through an endothelinB receptor, whereas the parathyroid hormone-stimulated increase in cyclic AMP is inhibited by endothelins. Phenotypic responses to endothelin-1 include changes in alkaline phosphatase activity, stimulation of osteocalcin and osteopontin message, stimulation of collagen and noncollagenous protein synthesis, inhibition of osteoclast motility and stimulation of prostaglandin-dependent resorption. Endothelin-1 also enhances the interleukin-1-induced increase in interleukin-6. Endothelins can also potentially affect calcium metabolism through their actions to inhibit the secretion of parathyroid hormone.
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PMID:Endothelin receptors, second messengers, and actions in bone. 760 88

Craniometaphyseal dysplasia (CMD) is a rare craniotubular bone dysplasia transmitted in autosomal dominant or recessive form. This disease is characterized by cranial bone hyperostosis and deformity of the metaphyses of the long bones. Using osteoclast-like cells formed from patient bone marrow cells, we investigated the pathophysiology of CMD in a 3-yr-old patient. Untreated bone marrow cells from the patient differentiated into osteoclast-like cells in vitro. These cells were shown to have vitronectin beta-receptors using a specific monoclonal antibody, i.e., 23C6 (CD51), which reacts with osteoclasts in human bone biopsy samples. However, the number of these osteoclast-like cells formed from the patient's bone marrow was only 40% of the normal controls. 1,25-dihydroxyvitamin-D3, bovine 1-34 parathyroid hormone, recombinant human interleukin-1 beta, recombinant human interleukin-6, or recombinant human macrophage colony-stimulating factor significantly increased, while salmon calcitonin significantly inhibited, the number of osteoclast-like cells. However, these cells could not resorb sperm whale dentin slices and lacked the osteoclast-reactive vacuolar proton pump as evidenced by a monoclonal antibody (E11). Western blot analysis using a monoclonal antibody to pp60c-src (327) revealed that protooncogene c-src expression by the platelets of the CMD patient was comparable to the normal control. These data suggest that: (a) the hyperostosis and the metaphyseal long bone deformity in the present CMD patient might be explained by osteoclast dysfunction due to impaired expression of the osteoclast-reactive vacuolar proton pump; and (b) a protooncogene c-src was not associated with the pathogenesis of the present CMD patient.
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PMID:Bone marrow-derived osteoclast-like cells from a patient with craniometaphyseal dysplasia lack expression of osteoclast-reactive vacuolar proton pump. 767 8

Bone is living tissue perpetually undergoing metabolism in a process known as remodelling, a sequence of cellular events occurring throughout the skeleton. The process is initiated in response to bone resorption by multinucleated osteoclasts. The capacity to stimulate osteoclastic activity is a property common to a multiplicity of hormones and cytokines--e g, parathyroid hormone, vitamin D, thyroxine, interleukin-1 and tumour necrosis factor. There is also a group of growth factors and cytokines, such as interleukin-6 and interleukin-11, that serve as stimulators of osteoclastic recruitment. Following bone resorption by osteoclasts, osteoblasts are recruited to the resorption lacuna, where they secrete osteoid which is then mineralised to form mature bone. The coupling of bone resorption and formation is governed by growth factors embedded in the mineralised bone matrix and released during resorption. These include transforming growth factor beta, insulin-like growth factor. Osteoporosis is caused by imbalance between the resorption and formation phases of the remodelling cycle.
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PMID:[Continuous remodeling of the skeleton. Growth factors and cytokines direct the activity]. 776 May 96

There is evidence suggesting some role of mononuclear cells at the resorptive site in bone remodeling. The possibility was therefore postulated that these cells might provide some signal for osteoclast formation. We examined the effects of human monocyte-conditioned medium (CM) on the formation of osteoclast-like cells from hemopoietic blast cells in the absence of stromal cells and unfractionated bone cells in the presence of stromal cells. In both culture systems, the osteoclast-like cell formation induced by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] or human parathyroid hormone (PTH)-(1-34) was significantly inhibited by adding 20% CM. The effects of monocyte-derived local regulators of bone turnover on osteoclast-like cell formation induced by 1,25(OH)2D3 or PTH were determined. Interleukin-6 (IL-6) inhibited osteoclast-like cell formation in both culture systems, whereas prostaglandin (PG) E2 significantly inhibited the formation only in the hemopoietic blast cell culture. The inhibitory effect of CM on osteoclast-like cell formation from hemopoietic blast cells was not observed when CM was prepared from monocytes pretreated with indomethacin. The inhibitory effect of CM and IL-6 on osteoclast-like cell formation in both culture systems was blocked by adding neutralizing IL-6 antibody. The present study demonstrated that CM inhibited osteoclast-like cell formation induced by 1,25(OH)2D3 and PTH presumably through the action of local regulators of bone turnover, such as IL-6 and PG. Our findings thus provide additional evidence that mononuclear cells play an important role at the resorptive site in bone remodeling.
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PMID:Role of interleukin-6 and prostaglandins in the effect of monocyte-conditioned medium on osteoclast formation. 781 Jun 28


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