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)

Cytosolic aminopeptidase P was obtained in highly purified form from human leukocytes by a four-step procedure. Buffy coats were the starting material. A M(r) of 140,000 was obtained by size-exclusion HPLC for the native enzyme. As shown by SDS/PAGE under reducing and denaturing conditions, the enzyme consisted of likely identical subunits with M(r) of 71,000. Purified aminopeptidase P cleaved off, specifically and efficiently, the N-terminal residues from peptides with N-terminal Xaa-Pro sequences. The penultimate proline was not replaceable by hydroxyproline, alanine and glycine in di-, tri- and tetrapeptides. Polyproline was not hydrolyzed. Dipeptides were cleaved (Arg-Pro, Phe-Pro > Trp-Pro > Pro-Pro) although slower than longer peptides. Cleavage was observed of several biologically active peptides; C-terminal fragment (residues 201-206) of C-reactive protein, oxytocin fragment Tyr-Pro-Leu-Gly, morphiceptin, peptide Gly-Pro-Arg-Pro (inhibitor of fibrin polymerization) and kentsin. In addition, cleavage of a protein, interleukin-6, was also demonstrated. Aminopeptidase P was maximally activated by Mn2+, and to a lesser extent by Co2+. The activity was optimal at pH 8. Ni2+, Zn2+ and especially Cd2+ caused marked inhibition. EDTA, 1,10-phenantroline and dithiothreitol were also inhibitory. Carbobenzoxy-phenylalanine, as well as several N-carbobenzoxy-proline-containing peptides, caused partial inhibition. The observed resistance of Gly-Pro, Pro-Gly, Pro-Phe and Pro-Ile to hydrolysis by the purified enzyme strongly indicates absence of known proline-specific dipeptidases in the aminopeptidase-P preparation.
 ...
PMID:Aminopeptidase P from human leukocytes. 144 89

The intracellular free calcium concentration ([Ca2+]i) in single gonadotropes was measured with a calcium-sensitive fluorescent dye indo-1 or fura-2 and a digital imaging fluorescence microscopic system to determine how interleukin-6 (IL-6) increases release of gonadotropins. IL-6 induced an increase in the basal [Ca2+]i or the amplitude of spontaneous oscillation of [Ca2+]i in gonadotropes in a mixed population. Gonadotropin-releasing hormone (Gn-RH) induced a biphasic increase in [Ca2+]i, a transient increase, and then a prolonged increase. These effects were inhibited by the absence of extracellular calcium or pretreatment with calcium channel blockers, cobalt or nifedipine. Next, purified gonadotropes were prepared by fluorescence-activated cell sorting and argon laser treatment of the cells. Gonadotropes labeled with anti-luteinizing hormone antibody were sorted by fluorescence-activated cell sorting and then cultured as monolayers for 24-48 h. In this way, gonadotropes were concentrated from 5-10% to 70-85% from whole pituitary cells. After relabeling with anti-luteinizing hormone antibody, 100% purified gonadotropes were obtained by killing other types of cells with an argon laser. Gonadotropin-releasing hormone induced almost the same responses of [Ca2+]i in the purified cell population as in the mixed cell population, but IL-6 did not affect [Ca2+]i in the purified gonadotropes. These results suggest that IL-6 affects calcium mobilization in gonadotropes indirectly via paracrine pathways.
 ...
PMID:Purification of gonadotropes and intracellular free calcium oscillation. Effects of gonadotropin-releasing hormone and interleukin 6. 200 97

We investigated the relationship between the toxic effects of metal wear particles and their ability to stimulate the release of inflammatory mediators implicated in bone resorption. In vitro studies were carried out with use of rat peritoneal macrophages, which were exposed to either cobalt-chromium-alloy or titanium-aluminum-vanadium particles, milled from the metal components of hip prostheses. The particles were in the size-range of, and at concentrations similar to, those found in the tissues surrounding failed prostheses in humans. The titanium-aluminum-vanadium particles showed little toxicity even at high concentrations, while the cobalt-chromium particles were very toxic. The titanium-aluminum-vanadium particles induced significantly more release of prostaglandin E2 than did the cobalt-chromium particles, and this was true for a wide range of concentrations. Exposure to titanium-aluminum-vanadium increased the release of prostaglandin E2, interleukin-1, tumor necrosis factor, and interleukin-6. In contrast, exposure to cobalt-chromium particles was associated with a decreased release of prostaglandin E2 and interleukin-6, and it had little effect on the release of interleukin-1 and tumor necrosis factor.
 ...
PMID:The differences in toxicity and release of bone-resorbing mediators induced by titanium and cobalt-chromium-alloy wear particles. 831 20

Angiogenesis, the formation of new blood vessels, is induced by various growth factors and cytokines that act either directly or indirectly. Vascular endothelial growth factor (VEGF) is a specific mitogen for vascular endothelial cells and therefore has a central role in physiological events of angiogenesis. Interleukin-6 (IL-6) expression on the other hand is elevated in tissues that undergo active angiogenesis but does not induce proliferation of endothelial cells. We demonstrate using Northern analysis that treatment of various cell lines with IL-6 for 6-48 h results in a significant induction of VEGF mRNA. The level of induction is comparable to the documented induction of VEGF mRNA by hypoxia or cobalt chloride, an activator of hypoxia-induced genes. In addition, it is demonstrated by transient transfection assays that the effect of IL-6 is mediated not only by DNA elements at the promoter region but also through specific motif(s) located in the 5'-untranslated region (5'-UTR) of VEGF mRNA. Our results imply that IL-6 may induce angiogenesis indirectly by inducing VEGF expression. It is also shown that the 5'-UTR is important for the expression of VEGF. The 5'-UTR of VEGF is exceptionally long (1038 base pairs) and very rich in G + C. This suggests that secondary structures in the 5'-UTR might be essential for VEGF expression through transcriptional and post-transcriptional control mechanisms.
 ...
PMID:Interleukin 6 induces the expression of vascular endothelial growth factor. 855 80

The wear particles of cobalt chrome alloy and titanium alloy have been implicated as a cause of aseptic loosening of prostheses. It is thought that their ability to induce either cell death or the release of mediators that induce bone resorption contributes to this loosening. This study was designed to test the hypothesis that these adverse biologic effects are due to wear particle corrosion at low pH after they have been phagocytosed by macrophages. Cobalt chrome alloy and titanium alloy particles of similar size and concentration to those found in the tissues surrounding failed prostheses were added to cultured rodent peritoneal macrophages. Treatment of macrophages with drugs that prevent a drop in pH within phagosomes significantly reduced the toxicity of phagocytosed cobalt chrome alloy particles. The same drugs also reduced the levels of prostaglandin E2 and interleukin-6 release induced by phagocytosed titanium alloy particles. When both types of particles were incubated at a low pH, similar to that encountered by phagocytosed particles, soluble products were released that induced the same effects as the particles themselves. These results show that enhanced corrosion of wear particles by phagocytic cells may contribute significantly to the adverse biologic effects of wear particles and identify drug therapies that may be investigated further.
 ...
PMID:Drug inhibition of the macrophage response to metal wear particles in vitro. 862

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.
 ...
PMID:Prosthetic metals interfere with the functions of human osteoblast cells in vitro. 918 23

Drug-induced uveitis is a relatively rare occurrence. For example, the patient database at the tertiary referral Uveitis Clinic at the Casey Eye Institute, Oregon Health Sciences University records an incidence of less than 0.5%. Despite this, the frequency of uveitis secondary to rifabutin therapy in AIDS patients has brought greater recognition to the potential role of medications as a cause of intraocular inflammation. A brief review of uveitis including its classification, causes, symptoms and signs is presented along with a review of systemic medications associated with uveitis. These medications include cidofovir, cobalt, diethylcarbamazepine, pamidronic acid (disodium pamidronate), interleukin-3 and interleukin-6, oral contraceptives, quinidine, rifabutin, streptokinase and sulfonamides. Other systemic medications may cause uveitis. Topical ocular medications such as beta-blockers and corticosteroids as well as other topical ocular medications have been associated with uveitis. Cidofovir, pamidronic acid, sulfonamides, rifabutin and topical metipranolol can 'probably' cause uveitis. The remainder of the medications discussed have a 'possible' cause-and-effect relationship with uveitis. Treatment begins with recognition of a drug-related event and usually subsequent avoidance of the drug. Therapy depends on the severity and likelihood of the reaction. Drug-induced uveitis is almost always reversible within weeks of discontinuation of the drug and treatment of the inflammation.
 ...
PMID:Drug-induced uveitis. Incidence, prevention and treatment. 930 54

Certain dental alloys have been claimed to cause gingival and periodontal inflammation. However, little information is available on the molecules mediating the mechanism of such an effect. Recently, a three-dimensional cell culture system consisting of human fibroblasts and keratinocytes has been introduced for evaluating the irritancy of cosmetic products, including the analysis of inflammatory mediators. In the present study the influence of pure metals and a high noble dental cast alloy upon cell viability and the synthesis of the proinflammatory mediator interleukin-6 was recorded in this in vitro skin equivalent model. The cultures were exposed to test specimens fabricated from copper, nickel, cobalt, zinc, palladium, tin, indium, a high noble cast alloy and a dental ceramic. Cell vitality was reduced after a 24 h exposure to copper (14-25% of untreated controls), cobalt (60%), zinc (63%), indium (85%), nickel (87%), and the heat treated and not heat treated high noble cast alloy (87%/90%). Dental ceramic, palladium and tin did not influence cell viability. Increased IL-6 levels were observed in cultures exposed to copper (5-19-fold compared to untreated controls), zinc (16-fold), cobalt (12-fold), nickel (10-fold) and palladium (4-fold). Other materials tested produced IL-6 levels comparable to those of untreated controls. Our findings suggest that metal ions are involved in proinflammatory activity at low toxicity and non-toxic levels as assessed by different biological endpoints.
 ...
PMID:Influence of metals on IL-6 release in vitro. 984 4

Cytokines produced by leukocytes in the periprosthetic membranes surrounding joint replacements have been implicated as causal agents in osteolysis and prosthetic loosening. In this study, we used an in vitro leukocyte culture system to monitor the response of leukocytes to various metal ions and their possible roles in the mechanism of aseptic loosening. Human peripheral leukocytes were isolated and incubated with various concentrations of Co2+, Cr3+, and Ti3+ ions. Leukocyte cell counts and the levels of the tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-6 (IL-6) and prostaglandin E2 (PGE2) released into the media were analyzed at 1 h, 3 h, and 1, 3, and 7 day intervals. The results showed that adding different metal ions into leukocyte cultures did not affect the cell counts. Exposure of leukocytes to Co2+ ion increased the release of TNF-alpha, IL-6, and PGE2. Exposure of leukocytes to Cr3+ ion did not increase the release of TNF-alpha but increased the secretion of IL-6 and PGE2. In contrast, exposure of the leukocytes to Ti3+ ions was associated with a decrease in the release of TNF-alpha and PGE2 and a minimal change in IL-6 noted after 7 days' culture. The present study elucidated the possible mechanisms involved in periprosthetic osteolysis and the inflammatory response of human leukocytes to metal ions. We found that cobalt ion is the most potent stimulant for cytokines and prostaglandin secretion by leukocytes. This elucidation, in combination with other efforts to reduce the generation of wear debris and metal ions, may improve the longevity of orthopedic implants.
 ...
PMID:Cytokine and prostaglandin E2 release from leukocytes in response to metal ions derived from different prosthetic materials: an in vitro study. 1061 28

Periprosthetic tissues observed at sites of loose total joint implants exhibit abundant macrophages, lymphocytes, fibroblasts and particulate debris. Macrophages phagocytose orthopaedic debris and release proinflammatory cytokines, chemokines, matrix metalloproteinases and other substances. In addition, other cell types present in tissues harvested from the bone-implant interface are thought to influence periprosthetic bone resorption. The present study examined the effects of polymethylmethacrylate (PMMA), cobalt chrome molybdenum alloy (CoCr), and titanium-alloy particle challenge on macrophages co-cultured with lymphocytes in vitro. Potential synergistic effects of lymphocytes on macrophage activation were determined by measuring interleukin-6 and tumor necrosis factor-alpha release following exposure to orthopaedic biomaterial particles. Exposure of macrophages or macrophages co-cultured with lymphocytes to all three types of particles resulted in increased release of interleukin-6 and tumor necrosis factor-alpha at 48 h, when compared to macrophages or macrophages co-cultured with lymphocytes, respectively, cultured in the absence of particles. Lymphocytes isolated from periprosthetic tissues secreted increased basal levels of cytokines relative to peripheral blood lymphocytes. Higher doses of PMMA and titanium-alloy particles stimulated increased levels of cytokine release in the macrophage and macrophage/lymphocyte groups. In contrast, a higher dose of CoCr particles (0.075% v/v) was not as effective as the 0.015% v/v dose, indicating probable CoCr toxicity. The macrophage/lymphocyte co-culture did not show synergism between the two types of cells with respect to cytokine release. T-cells at the bone-implant interface may alter the biological response to particulate debris.
 ...
PMID:In vitro reaction to orthopaedic biomaterials by macrophages and lymphocytes isolated from patients undergoing revision surgery. 1119


1 2 3 4 Next >>