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)

Fine particles in the air have been associated with increased mortality and morbidity. Particulate air pollution is a complex mixture which varies by region and includes a number of components including residual oil fly ash (ROFA), a byproduct of power plant and industry fuel-oil combustion. Human airway epithelial cells exposed to ROFA release inflammatory cytokines including interleukin (IL)-6, IL-8, and tumor necrosis factor. Expression of these genes is dependent upon pretranscriptional binding of cis regulatory elements, including nuclear factor kappaB (NF-kappaB). To investigate the role of NF-kappaB in the particulate-induced IL-6 response, we exposed human airway epithelial cells (BEAS-2B) to ROFA in vitro. ROFA stimulated a time- and dose-dependent increase in IL-6 messenger RNA (mRNA), which was preceded by the activation of nuclear proteins binding to the NF-kappaB sequence motif in the IL-6 promoter. Transient transfection of BEAS-2B cells with the 5' promoter region of the IL-6 gene linked to a luciferase reporter gene confirmed that NF-kappaB binding is necessary for the transcription of IL-6 mRNA. The IL-6 response was inhibited by the metal chelator deferoxamine and the free radical scavenger N-acetyl-L-cysteine, suggesting that the activation of NF-kappaB may be mediated through reactive oxygen intermediates generated by transition metals found in ROFA. Activation of NF-kappaB may therefore be a critical first step in the inflammatory cascade following exposure to particles generated by oil combustion.
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PMID:Air pollution particles induce IL-6 gene expression in human airway epithelial cells via NF-kappaB activation. 965 Nov 85

Elevated concentrations of ambient air particles can result in increased mortality and morbidity, especially in people with preexisting pulmonary disease. We postulate that in the inflammatory milieu of diseased lungs, alveolar macrophages (AMs) may be primed for enhanced responses to stimuli such as inhaled air particles. To test this hypothesis in vitro, we first cultured normal AMs with or without lipopolysaccharide (LPS). We then incubated the cells with particle suspensions (urban air particles (UAP, Washington, D.C.), residual oil fly ash (ROFA), concentrated respirable-size (PM2.5) air particles (CAPs), and inert TiO2) and compared rat and human AM production of the critical proinflammatory mediator, tumor necrosis factor (TNF). LPS priming amplified TNF production by both rat and human AMs in response to UAP and CAPs but not inert TiO2. There were also differences observed between rat and human AM responses to particle suspensions. Striking changes seen only in rat were cytotoxic effects of ROFA and diminished particle uptake in response to LPS priming. The potency of CAPs samples (which are collected on separate days) varied when comparing one day's sample with another. When centrifuged, the majority of bioactivity seen in particle suspensions (TNF release) remained within the pelleted fraction while the supernatant showed minimal bioactivity. The data suggest that AMs activated by extant pulmonary inflammation may promote further inflammation by an enhanced cytokine response to inhaled ambient air particles.
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PMID:Lipopolysaccharide priming amplifies lung macrophage tumor necrosis factor production in response to air particles. 1049 75

To determine whether the inflammatory effects of inhaled endotoxin could be prevented, we pretreated mice with synthetic competitive antagonists (975, 1044, and 1287) for lipopolysaccharide (LPS) before a LPS inhalation challenge. In preliminary studies, we found that these LPS antagonists did not act as agonists in vitro (THP-1 cells) or in vivo (after intratracheal instillation of 10 microg) and that these compounds (at least 1 microg/ml) effectively antagonized the release of tumor necrosis factor-alpha by LPS-stimulated THP-1 cells. Pretreatment of mice with 10 microg of either 1044 or 1287 resulted in a decrease in the LPS-induced airway hyperreactivity. Moreover, pretreatment of mice with 10 microg of 975, 1044, or 1287 resulted in significant reductions in LPS-induced lung lavage fluid concentrations of total cells, neutrophils, and specific proinflammatory cytokines compared with mice pretreated with sterile saline. Using residual oil fly ash to induce airway inflammation, we found that the action of the LPS antagonists was specific to LPS-induced airway disease. These results suggest that LPS antagonists may be an effective and potentially safe treatment for endotoxin-induced airway disease.
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PMID:Inhibition of LPS-induced airway hyperresponsiveness and airway inflammation by LPS antagonists. 1123 19

INTRODUCTION:To intrestigate the relationship between tumor necrosis factor-alphaand liver fibrosis in patients with chronic liver disease.METHODS:Radioimmunoassay was made in 20 patients with mild chronic hepatitis(CMH),20 patients with severe chronic hepatitis(CSH),51 patients with liver cirrhosis(LC)and 32-normal persons to determine the contents of tumor necrosis factor-alpha(TNF-alpha),laminin-(LN) and hyaluronate (HA) in serum.The changes in and relationship between TNF-alpha,LN and HA were analyzed.The TNF-alphaand collagen III were determined using mmunohistochemical studies in liver tissues from 32 persons including 7 normal persons,3 patients with MCH,5 patients with SCH and 17 with LC.RESULTS:TNF-alpha,LN and HA levels in serum of CSH and LC patients were significantly higher than those in healthy controls (SCH:1.11plus minus0.59 130.7plus minus17.2,219.1plus minus121.3;LC:0.92plus minus0.66,156.8plus minus31.7,400.5plus minus183.7,P<0.05-0.01),which increased gradually,and correlated positively with each other in all patients with liver diseases (n=91,gamma=0.3149 P <0.01).TNF-alpha contents-showed a remarkably positive correlation with HA and LN levels in CMH and CSH (LN:n=40,gamma=0.3404,P <0.05 HA n=40,gamma=0.3847 P <0.05).The total collagen content of MCH,SCH and LC increased gradually in liver biopsy specimens.The number of TNF-alphapositive cells increased significantly in liver tissues from patients with SCH and LC (62%;45%;P <0.01).TNF-alphapositive cells were mainly located in the periportal areas.CONCLUSION:TNF-alphamay be related to liver fibrosis,and might promote liver fibrosis.
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PMID:Relationship between tumor necrosis factor-alphaand liver fibrosis. 1181 20

Interactions between alveolar macrophages (AMs) and epithelial cells may promote inflammatory responses to air pollution particles. Normal rat AMs, the alveolar type II epithelial cell line RLE-6TN (RLE), or cocultures of both cell types were incubated with various particles (0-50 microg/ml) for 24 h, followed by assay of released TNF-alpha and MIP-2. The particles used included titanium dioxide (TiO2), alpha-quartz (SiO2), residual oil fly ash (ROFA), or urban air particles (UAP). For all particles, a dose-dependent increase in TNF-alpha and MIP-2 release was observed in AM+RLE co-cultures but not in RLE or AM monoculture. AM+RLE co-culture also synergistically enhanced basal levels of tumor necrosis factor (TNF)-alpha and macrophage inflammatory protein (MIP)-2. In contrast, when AMs were co-cultured with fibroblasts, basal and particle-induced TNF-alpha and MIP-2 were similar to levels found in AM monoculture. Particle uptake by AMs was similar in mono- or AM+RLE co-culture. Increased basal and particle-induced cytokine release were not observed when the AMs were physically separated from the RLE. This contact-dependent cytokine potentiation could not be blocked with anti-CD18/anti-CD54, arginine-glycine-aspartate (RGD) peptide, or heparin. We conclude that in vitro inflammatory responses to particles are amplified by contact-dependent interactions between AMs and epithelial cells. AM-epithelial co-culture may provide a useful model of in vivo particle effects.
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PMID:Lung macrophage-epithelial cell interactions amplify particle-mediated cytokine release. 1191 87

Insight into the mechanism(s) by which ambient air particulate matter (PM) mediates adverse health effects is needed to provide biological plausibility to epidemiological studies demonstrating associations between PM exposure and increased morbidity and mortality. Although in vitro PM studies provide an understanding of mechanisms by which PM affects pulmonary cells, it is difficult to extrapolate from in vitro to in vivo mechanisms of PM-induced lung injury. We examined in vivo mechanisms of lung injury generated by oil combustion particles. Rats were pretreated with dimethylthiourea (DMTU) before intratracheal instillation of residual oil fly ash (ROFA). Animals were examined by bronchoalveolar lavage for biomarkers of lung injury, and lung tissues were examined by immunohistochemical, biochemical, and molecular approaches to identify ROFA-induced alterations in intracellular signaling pathways and proinflammatory gene expression. Significant increases in pulmonary inflammation, cytotoxicity, activation of ERK mitogen-activated protein kinase (MAPK), and increases in mRNA levels encoding macrophage inflammatory protein (MIP)-2, interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, MCP-1 and matrilysin were observed. DMTU pretreatment inhibited ROFA-induced pulmonary inflammation, cytotoxicity, ERK MAPK activation, and cytokine gene expression. Our findings provide coherence with in vitro PM mechanistic information, allow direct in vitro to in vivo extrapolation, and demonstrate a critical role for oxidative stress in ROFA-induced lung injury and associated molecular pathology.
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PMID:Oxidative stress mediates air pollution particle-induced acute lung injury and molecular pathology. 1456 96

Local residents exposed to heavy falls of ash discharged by Mt. Sakurajima, an active volcano, have been reported to develop acute and chronic inflammation of the respiratory tract. The present study aimed to determine the primary cause of this inflammation using an experimental model. Wistar rats were exposed for 5 days (4 h/d) to air containing 100 mg/m3 volcanic ash (mass median aerodynamic diameter, 4.3 microm; geometric standard deviation, 1.7) with or without 1.5 ppm sulfur dioxide (SO2). The lungs were then lavaged, and mRNA was extracted from alveolar macrophages and assessed by reverse transcription-polymerase chain reaction (RT-PCR). In the lavage fluid, no change in cellularity or increase in the content of tumor necrosis factor (TNF)-alpha was detected. However, at 1 h following exposure, 80% of macrophages were seen to have phagocytosed the volcanic ash. This percentage was unchanged at 24 h after exposure. Profilin mRNA content of the macrophages was elevated, and c-jun mRNA was expressed. Alveolar macrophages exposed to volcanic ash and SO2, therefore, are likely to have some inflammatory and fibrogenic potential.
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PMID:c-jun mRNA expression and profilin mRNA amplification in rat alveolar macrophages exposed to volcanic ash and sulfur dioxide. 1462 Jun 66

The mechanisms of susceptibility to particle-induced lung injury are not clearly understood. To evaluate the contribution of genetic background to pulmonary pathogenesis, we compared the lung injury responses to residual oil fly ash (ROFA) in inbred mouse strains and calculated heritability estimates. Significant interstrain (genetic) variation was observed in ROFA-induced lung inflammation and hyperpermeability phenotypes; broad-sense heritability ranged from approximately 0.43 to 0.62, and the coefficient of genetic determination ranged from 0.28 to 0.45. C3H/HeJ (HeJ) mice were most resistant to the ROFA-induced injury responses. This was particularly important, as HeJ mice contain a dominant negative mutation in Toll-like receptor-4 (Tlr4). We then characterized ROFA-induced injury and TLR4 signaling in HeJ mice and its coisogenic strain C3H/HeOuJ (OuJ; Tlr4 normal) to understand the potential role of Tlr4 in this model. ROFA-induced lung injury was significantly greater in OuJ mice compared with HeJ mice. ROFA also significantly enhanced transcript and protein levels of lung TLR4 in OuJ but not in HeJ mice. Greater activation of downstream signal molecules (i.e., MYD88, TRAF6, IRAK-1, NF-kappaB, MAPK, AP-1) was observed in OuJ mice than in HeJ mice before the development of ROFA-induced pulmonary injury. Putative TLR4-dependent inflammatory genes that were differentially induced by ROFA in the two strains include interleukin-1beta and tumor necrosis factor-alpha. Results support an important contribution of genetic background to particle-mediated lung injury, and Tlr4 is a candidate susceptibility gene.
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PMID:Role of Toll-like receptor-4 in genetic susceptibility to lung injury induced by residual oil fly ash. 1578 98

Epidemiological data show an association between exposure to elevated levels of particulate matter (PM), in particular the fine fraction (<2.5 microm in diameter), and an increase in cardiovascular mortality and respiratory symptoms. The aim of this study was to compare the in vitro toxicity of coarse and fine particulate matter collected with a cascade impactor during winter in an urban area of Rome in relation to their physicochemical characterization (size distribution and chemical composition) as assessed by analytical electron microscopy (SEM/EDX). The X-ray microanalysis data of single particles of coarse and fine matter were analyzed by hierarchical cluster analysis to determine the principal component of the two granulometric fractions. The main chemical difference between the two fractions was the greater abundance of carbonaceous particles in the fine fraction. We compared the ability of coarse and fine fractions, carbon black (CB), and residual oil fly ash (ROFA) to induce arachidonic acid release and tumor necrosis factor-alpha (TNF-alpha) production in the monocytic-macrophagic RAW 264.7 cell line at concentrations of 30 and 120 microg/mL. Our results showed that CB and ROFA were consistently less effective than both fractions of urban particles at inducing an inflammatory reaction in RAW 264.7 cells. Both PM fractions dose-dependently increased TNF-alpha production in RAW 264.7 cells after 5 and 24h of incubation, and only the TNF-alpha production induced by coarse particles at 30 microg/mL decreased significantly (P<0.01) after 24h of treatment. In our in vitro model the winter fine fraction was more reactive than the winter coarse fraction, in contrast to a previously examined summer sample. In the summer sample, coarse particles produced higher levels of inflammatory mediators than fine particles and the CB was consistently less effective than the urban particles. The different behaviors between summer and winter urban fractions may be due to their different physicochemical characteristics; in fact, the comparison of the two samples' characterization by SEM/EDX and X-ray photoelectron spectroscopy (XPS) analysis showed that in winter the carbonaceous particles are more abundant than in summer and that winter particles carry a greater quantity of organic compounds. We suggest that the higher concentration of organic compounds on fine carbonaceous particles may partially explain the higher activation of RAW 264.7 cells by fine particles.
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PMID:Winter urban air particles from Rome (Italy): effects on the monocytic-macrophagic RAW 264.7 cell line. 1630 76

Skeletal abnormalities, low bone mass, bone deformities, and bone fractures increase the risk of osteoporosis and osteoarthritis, which are of concern from both a public standpoint and a cost-of-care burden standpoint. Arginine silicate inositol complex (ASI; Arg = 49.47%, silicone = 8.2%, inositol = 25%) is a novel, bioavailable source of Si and Arg and one that offers potential benefits for vascular and bone health. Skeletal abnormalities and architectural deterioration of bone tissue are common under hot climate conditions in the poultry industry. In this study, we evaluated the effects of ASI supplementation on performance and bone mineral density (BMD) in Japanese quail (Coturnix coturnix japonica) exposed to the high ambient temperature of 34 degrees C. The birds (n = 180; 10 d old) were randomly assigned to 6 treatment groups consisting of 10 replicates of 3 birds. Birds were kept in wire cages in a temperature-controlled room at either 22 degrees C (thermoneutral; TN) or 34 degrees C (heat stress; HS) for 8 h/d (0900 to 1700 h until the end of study) and were fed a basal (control) diet or the basal diet supplemented with either 500 or 1,000 mg of ASI/kg of diet. Heat exposure decreased performance and bone mineralization when the basal diet was fed (P = 0.001). The ASI supplement had no effect on feed intake, BW, feed efficiency, and carcass traits (P > 0.05) in quails reared under TN or HS conditions. The BMD was significantly improved by ASI supplementation in both TN and HS groups [0.72 (TN) vs. 0.60 (HS); P < or = 0.05]. Serum osteocalcin, dehydroepiandrosterone concentrations, and alkaline phosphatase activity increased, whereas tumor necrosis factor-alpha and Creactive protein concentrations decreased, as dietary ASI supplementation increased in quail reared under HS. This improvement was linear with increased doses of supplement (P = 0.001). In the ASI group, the amount of Ca, P, Mg, and Mn in the excreta decreased (P < or = 0.05), and the concentrations of these minerals in tibia ash increased in quail reared under HS conditions (P < or = 0.05). In conclusion, ASI supplementation to the basal diet significantly improved bone mineralization in quail and did not impact feed consumption, BW gain, or feed efficiency.
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PMID:Dietary arginine silicate inositol complex improves bone mineralization in quail. 1655 80


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