Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0205700 (ash)
 15,125 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The object of this research is to investigate the influence of interleukin-1 (IL-1) on heterotopic ossification (HO) induced by bone morphogenetic protein (BMP). Adult mice were implanted with doses of 1, 2, 5, and 10 mg of BMP. Several local injections of 10, 100, and 1000 units of a recombinant IL-1 beta (rIL-1 beta) were administered during the morphogenetic phase of development, starting a day before operation until one week postoperation. While IL-1 acts principally on cell proliferation, BMP primarily shows cell differentiation in the form of HO. BMP-induced HO is quantitated by computer X-ray image scanning, bone ash weight, alkaline phosphatase activity, and histological methods. The area of human BMP-induced HO was completely abolished by injections of polyclonal and monoclonal anti-IL-1 antibody. Monoclonal antibody did not cross-react with the same efficiency as polyclonal with bovine BMP. Polyclonal anti-IL-1 antibody totally neutralizes bovine BMP activity. IL-1-enhanced BMP induced HO and increased the volume of new bone in a statistically significant increment.
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PMID:Experimental heterotopic bone formation induced by bone morphogenetic protein and recombinant human interleukin-1B. 326 6

Interleukin-1 (IL-1) is a monokine that exerts multiple biological activity, including immunity and inflammation. Moreover, IL-1 is involved in Ca2+ release causing hypercalcemia and bone resorption. Recently, a 22 kDa natural inhibitor to IL-1 called interleukin-1 receptor antagonist (IL-1ra) has been described in human fluids, which specifically binds IL-1 alpha or IL-1 beta receptors. In this study, we found that experimental granuloma induced by subcutaneous injections (0.2 ml) of potassium permanganate (KMnO4) 1:40 saturated crystal solution, after 7 days was strongly inhibited in size, weight and calcium content (measured as dry ash weight by incineration of granuloma tissue) compared with untreated controls, in mice treated intraperitoneally with IL-1ra (20 micrograms/bolus) given twice; the first at the same time of the induction of the granuloma and the second 24 hours later. In addition, leukotriene B4 and prostaglandin E2 were also inhibited in fresh granuloma of mice treated with IL-1ra. Taken together, these findings conclude for the first time, that the accumulation of calcium in chronic inflammatory states is strongly inhibited by IL-1ra, which decreases tissue calcergy and can potentially be useful for the treatment of calcium-related inflammatory diseases and malignancy-associated hypercalcemia.
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PMID:Interleukin-1 receptor antagonist inhibits calcium accumulation in in vivo chronic granuloma induced by potassium permanganate. 838 44

Elevated levels of ambient particulate matter (PM(10)) have been associated with increased cardiopulmonary morbidity and mortality. We previously showed that the deposition of particles in the lung induces a systemic inflammatory response that includes stimulation of the bone marrow. This marrow response is related to mediators released by alveolar macrophages (AM) and in this study we measured cytokines produced by human AM exposed to ambient particles of different composition and size. Identified cytokines were also measured in the circulation of healthy young subjects exposed to air pollutants during the 1997 Southeast Asian forest fires. Human AM were incubated with particle suspensions of residual oil fly ash (ROFA), ambient urban particles (EHC 93), inert carbon particles, and latex particles of different sizes (0.1, 1, and 10 microm) and concentrations for 24 h. Tumor necrosis factor-alpha (TNF-alpha) increases in a dose-dependent manner when AM were exposed to EHC 93 particles (p < 0.02). The TNF response of AM exposed to different sizes of latex particles was similar. The latex (158 +/- 31%), inert carbon (179 +/- 32%), and ROFA (216 +/- 34%) particles all show a similar maximum TNF response (percent change from baseline) whereas EHC 93 (1,020 +/- 212%, p < 0.05) showed a greater maximum response that was similar to lipopolysaccharide (LPS) 1 microg/ml (812 +/- 320%). Macrophages incubated with an optimal dose of EHC 93 particles (0.1 mg/ml) also produce a broad spectrum of other proinflammatory cytokines, particularly interleukin (IL)-6 (p < 0.01), IL-1 beta (p < 0.05), macrophage inflammatory protein-1 alpha (MIP-1 alpha) (p < 0.05), and granulocyte macrophage colony-stimulating factor (GM-CSF) (p < 0.01) with no difference in concentrations of the anti-inflammatory cytokine IL-10 (p = NS). Circulating levels of IL-1 beta, IL-6, and GM-CSF were elevated in subjects exposed to high levels of PM(10) during an episode of acute air pollution. These results show that a range of different particles stimulate AM to produce proinflammatory cytokines and these cytokines are also present in the blood of subjects during an episode of acute atmospheric air pollution. We postulate that these cytokines induced a systemic response that has an important role in the pathogenesis of the cardiopulmonary adverse health effects associated with atmospheric pollution.
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PMID:Cytokines involved in the systemic inflammatory response induced by exposure to particulate matter air pollutants (PM(10)). 1154 40

Metabolic and cognitive alterations occur during hyperammonemia. Here, we report that chronic hyperammonemia also leads to increased sensitivity to LPS. Sparse-fur mice were challenged i.p. with LPS or saline control and then tested for motivation to investigate a novel juvenile over 24 h. Cytokine, ammonia, and urea concentration were quantified at the peak of sickness (2 h post injection). Chronic hyperammonemic Otc(spf-ash) mice displayed more pronounced and prolonged sickness behavior in response to LPS (P=0.02). LPS significantly (P<0.0001) increased plasma concentrations of TNFalpha, IL-1 beta, IL-6, IL-15, IL-9, IL-2, IL-1 alpha, IL-1 beta, Rantes, MIP1 alpha, MIP1 beta, MCP-1, KC, GM-CSF, G-CSF, Eotaxin, IL-13, and IL-12 in both wild type and Otc(spf-ash) mice. No significant genotype/treatment interactions (P>0.1) were detected for any cytokine. Adult Otc(spf-ash) mice (168+/-41 microM) had four times higher plasma ammonia compared to wild type mice (40 +/- 6 microM) (P=0.002). Two hours after LPS injection, plasma ammonia concentrations tended (P=0.08) to decrease in both wild type and Otc(spf-ash) mice. Learning and memory behaviors were assessed in mice under basal conditions to determine the impact of chronic hyperammonemia on cognition. Otc(spf-ash) mice performed significantly poorer in the two trial Y-maze (P=0.02) and the Morris water maze (P=0.001) than their littermate wild type controls. Taken together, these data indicate that chronic hyperammonemia results in impaired cognition and creates a state of LPS hypersensitivity.
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PMID:Hyperammonemia increases sensitivity to LPS. 1649 29