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)

After hip prosthetic replacement, a progressive enlargement in the radiolucent area has often been observed around the implant, leading to loosening of the prosthesis. The purpose of this study was to investigate the mechanism of the radiolucent area formation. Radiolucent areas can be classified into either linear type or the erosive type, and these two types were compared histologically and biochemically. Interface membranes were obtained from patients at the time of surgery for revision of either cemented THA or cementless bipolar endprosthetic replacement. Histological specimens were stained by H.E., tartrate-resistant acid phosphate, and by the immunohistochemical reagents anti-macrophage antibody (CD 68), anti-T-lymphocyte (CD 3, CD 4, CD 8, CD 43), anti-interleukin-1 beta polyclonal antibody, anti-interleukin-6 polyclonal antibody, and anti-tumor necrosis factor-alpha polyclonal antibody. Biochemically, interleukin-1 beta, IL-6, IL-8, TNF-alpha were assayed by ELISA in the supernatant of homogenized samples and in organ culture media. Prostaglandin E2 was assayed by radioimmunoassay. The interfaces of the erosive type contained more debris (cement, high density polyethylene and metal), macrophages and multinucleated giant cells than the linear type. The interfaces of the linear type showed mainly fibrosis and necrosis. The levels of IL-6 and IL-8 in the homogenates and culture media from the erosive type were significantly higher than those from the linear type. We concluded that the bone resorption around the implant after hip prosthetic replacement occurred by two different pathways. One pathway involved the stimulation of macrophages by various debris and micromovement to form foreign body granulomas, which produced cytokines, prostaglandin E2 and metalloproteinase to resorb bone. The erosive type would arise from this pathway. The other possible mechanism involved a biomechanically unstable implant which caused bone necrosis probably by mechanical stress. The linear type may arise from this pathway.
 ...
PMID:[Mechanism of the radiolucence around the implant after hip prosthetic replacement]. 855 Oct 95

Platelet activating factor (PAF) is a potent mediator of allergic and inflammatory reactions in different pathological conditions. During recent years there has been increasing evidence that PAF can play an important role in the pathogenesis of arthritis. The PMN proteinases make an important contribution to the final tissue joint destruction in arthritis. In a rabbit model of acute crystal arthritis, we have compared the anti-inflammatory effect of two new molecules: BN 50727 with anti-PAF activity, and BN 50548 an inhibitor of PMN proteinases. These molecules were administered dissolved in DMSO at doses of 6 mg/kg three times daily i.p., beginning 24 h before the induction of arthritis. Compared with the untreated animals those receiving the drugs, presented a significant diminution in: (1) the synovial fluid volume; (2) the amount of cells infiltrating the joint cavity and the synovial membrane; and (3) the PGE2 concentration. Furthermore, in both groups of treated rabbits there was a significant decrease in synovial IL-6 concentration and in C-reactive protein serum levels and an important decline of histopathological score. The treatment with BN 50548 induced a significant reduction of TNF levels in the synovial fluid vs DMSO-treated and untreated rabbits. These results further strengthen that in an acute experimental arthritis model, molecules with capacity to antagonize the in vivo action of PAF have an anti-inflammatory effect reflecting an important role for this mediator in the pathogenesis of arthritis. We have also seen that an inhibitor of proteinases is capable of improving the joint inflammation apparently through a decrease in tumor necrosis factor (TNF) and interleukin-6 (IL-6) synovial levels. Furthermore, the proteinase inhibitor treatment preserves the loss of articular proteoglycan content, in an acute arthritis model. In conclusion, BN 50727 and BN 50548, two compounds with PAF antagonist and antiproteinase activity, respectively exert an anti-inflammatory effect in an experimental model of acute urate crystal arthritis, probably due to a decrease in TNF alpha and IL-6 synthesis.
 ...
PMID:Anti-inflammatory effect of a PAF receptor antagonist and a new molecule with antiproteinase activity in an experimental model of acute urate crystal arthritis. 882 9

The purpose of this study was to further define the cellular response to titanium and polymethylmethacrylate (PMMA) particles in aseptic loosening, and to determine if the use of pamidronate may be effective in inhibiting bone resorption associated with this response. Macrophages and osteoblasts were cocultured to simulate the environment around an aseptically loose prosthesis. Macrophages were plated on the bottom of six well plates and osteoblasts were plated on culture dish inserts, and placed into the wells with the macrophages. Incubation of macrophages with PMMA in this system led to release of prostaglandin E (PGE2), granulocyte macrophage-colony stimulating factor (GM-CSF), and interleukin-6 (IL-6). Incubation with titanium led to release of tumor necrosis factor (TNF) and IL-6. Exposure of calvaria to media from cells exposed to either PMMA or titanium led to release of calcium 45. Incubation of calvaria with pamidronate was able to inhibit release of calcium 45 associated with exposure to the macrophage/osteoblast/particle conditioned medium. Bone resorption at the interface between implant and bone is a consistent feature leading to loosening of orthopedic implants. By inhibiting bone resorption associated with the inflammatory response to implant particulates, pamidronate or other bisphosphonates may have clinical utility in the treatment or prevention or aseptic loosening.
 ...
PMID:Inflammatory response to implant particulates in a macrophage/osteoblast coculture model. 884 7

Prostaglandins (PGs) and cytokines, such as interleukin-1 (IL-1) and interleukin-6 (IL-6), have been implicated in the etiopathology of various inflammatory and degenerative disorders, including Alzheimer's disease (AD) and prion diseases. Nonsteroidal antiinflammatory drugs (NSAIDs), potent inhibitors of PG synthesis, appear to be beneficial in the treatment of AD. To assess whether PGs are able to induce IL-6 synthesis in cells of the CNS, IL-6 mRNA and protein syntheses were measured in a human astrocytoma cell line after stimulation with different PGs. PGE1 and PGE2, but not PGD2 and PGF2 alpha, led to a rapid and transient induction of IL-6 mRNA, followed by IL-6 protein synthesis. Furthermore, PGE2 potentiated IL-1 beta-induced IL-6 mRNA synthesis. These results are discussed with respect to the participation of PGs in neurodegenerative diseases (and its inhibition by NSAIDs) by affecting cytokine expression.
 ...
PMID:Prostaglandin E2 induces interleukin-6 synthesis in human astrocytoma cells. 900 59

The objective of this study was to analyse the effects of 4 nonsteroidal anti-inflammatory drugs (NSAIDs) on the production of beta-glucuronidase (beta-glu), tumour necrosis factor alpha (TNF alpha), interleukin-6 (IL-6), interleukin-1 (IL-1) and prostaglandin E2 (PGE2) by lipopolysaccharide (LPS)-stimulated equine synoviocytes. The agents studied were flunixin, tolfenamic acid, S(+)ketoprofen (KTP) and R(-)ketoprofen. LPS-induced release of beta-glu from synoviocytes was inhibited in a concentration dependent manner by all 4 compounds, tolfenamic acid being the most potent. Of the 2 KTP enantiomers, S(+)KTP exerted the greatest inhibitory effect. Tolfenamic acid and flunixin increased the production of IL-6-like activity by LPS-stimulated synoviocytes only at the highest concentration studied (1000 mumol/l). Lower concentrations produced no effect on IL-6. Flunixin, tolfenamic acid and S(+)KTP produced statistically significant and concentration related increases in the release of IL-1-like activity by LPS-stimulated synoviocytes. Prostaglandin E2 synthesis was markedly inhibited in a concentration dependent manner by the 4 NSAIDs. However, R(-)KTP was effective only at the highest concentrations investigated (1000 and 100 mumol/l). The present findings are compatible with the possibility that longterm use of NSAIDs in arthropathies, by removing the regulator role of PGE2 on IL-1 synthesis, might enhance the pathological process of cartilage degeneration.
 ...
PMID:Effects of flunixin, tolfenamic acid, R(-) and S(+) ketoprofen on the response of equine synoviocytes to lipopolysaccharide stimulation. 904 96

Interleukin-6 (IL-6) induces osteoclast-like cell (osteoclast) formation in a dose-dependent fashion in cocultures of mouse bone marrow cells and osteoblastic cells when soluble IL-6 receptor (sIL-6R) is present. Simultaneous treatment with submaximal doses of IL-1alpha and IL-6 with sIL-6R caused marked induction of osteoclast formation and PGE2 synthesis. These effects were suppressed by adding neutralizing antibodies against IL-1alpha or IL-6R and were totally abolished by adding nonsteroidal antiinflammatory drugs, such as indomethacin and a selective cyclooxygenase-2 (COX-2) inhibitor (NS398). In mouse osteoblastic cells, both IL-1alpha and IL-6 with sIL-6R markedly induced messenger RNA expression of COX-2, but not COX-1, as determined by Northern blot analysis, and luciferase activity in cells stably transfected with a COX-2 promoter-luciferase fusion construct. IL-6 and sIL-6R, when added separately, did not stimulate COX-2 messenger RNA expression. Simultaneous addition of IL-1alpha and IL-6 with sIL-6R to osteoblast cultures cooperatively induced transcription of COX-2, which was associated with a marked increase in COX activity measured by the conversion of arachidonic acid into PGE2. The increased PGE2 synthesis by osteoblasts may play an important role in osteoclastogenesis induced by submaximal doses of IL-1 and IL-6.
 ...
PMID:Transcriptional induction of cyclooxygenase-2 in osteoblasts is involved in interleukin-6-induced osteoclast formation. 916 25

1. The effect of dexamethasone, lipocorton-1(2-26) and an antiserum to lipocortin-1(2-26) (LCPS1) upon the hyperalgesic activities in rats of carrageenin, bradykinin, tumour necrosis factor alpha (TNF alpha), interleukin-1(2), interleukin-6 (IL-6), interleukin-8 (IL-8), prostaglandin E beta (PGE2) and dopamine were investigated in a model of mechanical hyperalgesia. 2. Hyperalgesic responses to intraplantar (i.pl.) injections of carrageenin (100 micrograms), bradykinin (500 ng), TNF alpha (2.5 pg), IL-1 beta (0.5 pg), and IL-6 (1.0 ng), but not responses to IL-8 (0.1 ng), PGE2 (100 ng) and dopamine (10 micrograms), were inhibited by pretreatment with dexamethasone (0.5 mg kg-1, subcutaneously, s.c., or 0.04-5.0 micrograms/paw). 3. Inhibition of hyperalgesic responses to injections (i.pl.) of bradykinin (500 ng) and IL-1 beta (0.5 pg) by dexamethasone (0.5 mg kg-1, s.c.) was reversed by LCPS1 (0.5 ml kg-1, injected s.c., 24 h and 1 h before hyperalgesic substances) and hyperalgesic responses to injections (i.pl.) of bradykinin (500 ng), TNF alpha (2.5 pg) and IL-1 beta (0.5 pg), but not responses to PGE2 (100 ng), were inhibited by pretreatment with lipocortin-1(2-26) (100 micrograms/paw). Also, lipocortin-1(2-26) (30 and 100 micrograms ml-1 and dexamethasone (10 micrograms ml-1) inhibited TNF alpha release by cells of the J774 (murine macrophage-like) cell-line stimulated with LPS (3 micrograms ml-1), and LCPS1 partially reversed the inhibition by dexamethasone. These data are consistent with an important role for endogenous lipocortin-1(2-26) in mediating the anti-hyperalgesic effect of dexamethasone, with inhibiton of TNF alpha production by lipocortin-1(2-26) contributing, in part, to this role. 4. Although arachidonic acid by itself was not hyperalgesic, the hyperalgesic response to IL-1 beta (0.25 pg, i.pl.) was potentiated by arachidonic acid (50 micrograms) and the potentiated response was inhibited by dexamethasone (50 micrograms, i.pl.) and lipocortin-1(2-26) (100 micrograms, i.pl.). Also, lipocortin-1(2-26) (30 and 100 micrograms ml-1) inhibited/abolished PGE2 release by J774 cells stimulated with LPS (3 micrograms ml-1). These data suggest that, in inflammatory hyperalgesia, inhibition of the induction of cyclo-oxygenase 2 (COX-2), rather than phospholipase A2, by dexamethasone and lipocortin-1(2-26) accounts for the anti-hyperalgesic effects of these agents. 5. The above data support the notion that induction of lipocortin by dexamethasone plays a major role in the inhibition by dexamethasone of inflammatory hyperalgesia evoked by carrageenin, bradykinin and the cytokines TNF alpha, IL-1 beta and IL-6, and provides additional evidence that the biological activity of lipocortin resides within the peptide lipocortin-1(2-26). Further, the data suggest that inhibition of lipocortin-1(2-26) of eicosanoid production by COX-2 also contributes to the anti-hyperalgesic effect of lipocortin-1.
 ...
PMID:Role of lipocortin-1 in the anti-hyperalgesic actions of dexamethasone. 922 44

At the interface between a prosthetic implant and bone, macrophage interaction with particulate wear debris is a key event in the initiation of localized bone resorption, leading to aseptic loosening of the prostheses. Numerous investigators have reported that macrophages release a variety of cytokines and mediators including tumor necrosis factor, interleukin-1, prostaglandin E2, and interleukin-6 when they are stimulated with particulate wear debris. In this study, we have demonstrated that macrophages stimulated with particulate debris are also capable of releasing in copious amounts a key inflammatory chemical, nitric oxide. This release of nitric oxide was dependent upon the period of culture and the type and dosage of the challenging particles. Titanium-alloy particles were the most stimulatory, followed by commercially pure titanium and polymethyl-methacrylate. While the role of nitric oxide in osteolysis is not clearly understood, the literature suggests that it may be a key mediator in inhibiting DNA synthesis, in cell proliferation, and in stimulating PGE2 release. This finding enhances our understanding of the sequence of events occurring at the bone-implant interface during wear debris-mediated osteolysis, and exposes potential avenues to interrupt this sequence.
 ...
PMID:Nitric oxide release by macrophages in response to particulate wear debris. 965 21

Prostaglandin E2 (PGE2) is an abundant eicosanoid in bone that has been implicated in a number of pathological states associated with bone loss. Interleukin-6 (IL-6) is a cytokine that plays a critical role in bone remodeling and appears to act as a downstream effector of most bone-resorbing agents. In light of the evidence that PGE2 induces IL-6 in the bone environment, this study was designed to investigate whether PGE2 regulated IL-6 expression by osteoblasts. Here we demonstrate that PGE2 is a potent inducer of IL-6 production by fetal rat osteoblasts and synergizes with lipopolysaccharide to enhance IL-6. We show that PGE2 stimulates the activity of the IL-6 promoter in osteoblasts, suggesting that PGE2 controls IL-6 gene expression at least at the transcriptional level. Moreover, we show that PGE2-mediated IL-6 induction is prevented by the cAMP antagonist, Rp-cAMP, and the protein kinase A (PKA) inhibitors, KT5720 and H89. Thus, our data indicate that PGE2 involves the cAMP-PKA signaling pathway to regulate IL-6 gene expression in osteoblasts.
 ...
PMID:Regulation of interleukin-6 production by prostaglandin E2 in fetal rat osteoblasts: role of protein kinase A signaling pathway. 966 Oct 73

Ultraviolet-A radiation has weak effects on the release of inflammatory mediators by skin cells due to the poor overlap between UVA wavelengths and the absorption spectra of the relevant chromophores of key biomolecules. However, this situation could be very different in the presence of a photosensitizing drug. To investigate this issue, we have irradiated human skin cells (keratinocytes and fibroblasts) in the presence of fenofibric acid (the active phototoxic metabolite of fenofibrate). The results of this research show a dual effect on the production/release of inflammatory mediators: the synthesis of the proinflammatory cytokine interleukin-6 becomes strongly inhibited at photosensitizer concentrations that clearly stimulate the production of prostaglandins (PGE2) by skin cells. We have found evidences showing that the de novo synthesis of cytokines is inhibited in photosensitized cells due to the fact that cellular mRNA is degraded. Interestingly, when the medium taken from irradiated cultures is added to nonexposed cells, a significant stimulation of cytokine synthesis is observed that can be inhibited by anti-PGE2 antibodies. These observations may be relevant in vivo, where prostaglandins released by photosensitized skin cells could stimulate cytokine synthesis by underlying, nonirradiated cells.
 ...
PMID:Release of inflammatory mediators (PGE2, IL-6) by fenofibric acid-photosensitized human keratinocytes and fibroblasts. 974 88


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