Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0037116 (silicosis)
 1,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to provide scientific information on the prevention and treatment of silicosis, studies about changes of silicotic collagen in lungs were carried out. In this paper, we present experiments about the structural changes of collagen in silicotic lungs of rats and patients. These included electron microscopy, circular dichroism and infrared spectroscopy studies of collagen fibers. The results indicated that fibers of silicotic collagen were shorter in length, smaller in diameter and decreased in alpha-helix content. The -Si-O-R- group and -OH group were found increased and -C-C- backbone shortened. The increase of -Si-O-R- group indicated that silica formed linking bridges between collagens which may be the cause of progressive enlargement of nodules.
 ...
PMID:Studies on structural changes of collagen in silicosis. 770 60

In the screening tests of drugs for silicosis in our laboratory, we found that TT, a type of alkaloid isolated from Stephania tetrandra, could inhibit the development of experimental silicosis of rats and the synthesis of collagen in rat lung. Chest X-rays of silicotic patients treated with TT for 1-3 years showed obvious changes. The silicotic nodules became smaller and shadows became clearer. PVNO was proved to have anti-silicotic effect on animal and clinically. This presentation reports the effect of them on collagen mRNA. Dot blot results showed that alpha 1 (I) and alpha 1 (III) mRNA levels increased significantly at 60 and 120 days after the rats were exposed to silica dust. The mRNA levels went down at 1 and 3 months after treated by TT and PVNO. In situ hybridization observation revealed that the silver grains of Type I and Type III collagen were scattered within the fibroblasts in cellular nodules and in thickened interstitium of silicosis tissue. The amounts of mRNA silver grains decreased in the lung tissue treated by TT and PVNO. It was suggested that TT and PVNO may inhibit the gene expression of collagen during silicosis.
 ...
PMID:The effects of tetrandrine (TT) and polyvinylpyridine-N-oxide (PVNO) on gene expression of type I and type III collagens during experimental silicosis. 784 48

To evaluate components of the pulmonary cellular response to inhaled silica that might be determinants of progression to fibrosis, we developed a model of the early stages of chronic human silicosis. Groups of mice were subacutely exposed either to alpha-quartz or to nonfibrogenic titanium dioxide dust as a control. Induction of lesions by inhaled silica was dependent upon the size distribution and dose of the particles. A novel observation was that low intensity exposure to silica evoked reversible inflammatory lesions that were characterized by focal aggregation of particle-laden alveolar macrophages near terminal airways. In contrast, higher intensity exposure elicited progressive pulmonary inflammation, including a significant perivascular influx of T-lymphocytes early in the response. The airspace inflammatory lesions exhibited a statistically significant decline in numerical density over time. Meanwhile, deposition of collagen was observed at perivascular locations, which were anatomically distinct from the initial foci of inflammation, and the numerical density of fibrotic lesions increased significantly with time. We speculate that this pattern of response might be related to alveolar clearance mechanisms being overwhelmed, followed by translocation and sequestration of particles in the interstitium, subsequently leading to T-lymphocyte recruitment and ultimately to the development of fibrosis.
 ...
PMID:Pulmonary inflammation and fibrosis following subacute inhalational exposure to silica: determinants of progression. 826 48

In vitro and in vivo animal studies, as well as human investigations, strongly support the role of macrophage products in the development and progression of silicosis and coal workers' pneumoconiosis. Such products include enzymes and reactive oxygen species which may cause lung damage; cytokines which recruit and/or activate polymorphonuclear leukocytes and thus result in further oxidant damage to the lung; and fibrogenic factors which induce fibroblast proliferation and collagen synthesis. This mechanistic understanding of pulmonary disease should assist in developing strategies for prevention and treatment.
 ...
PMID:How silicosis and coal workers' pneumoconiosis develop--a cellular assessment. 838 79

We have evaluated, in an experimental model of silicosis in guinea pigs, if the presence of collagenolytic activity in bronchoalveolar lavage (BAL) fluid reflects the collagen catabolism in lung parenchyma. We measured simultaneously BAL collagenase activity, using as substrate [3H]type I collagen, and lung collagenolytic activity by the tissue pellet assay. Animals (n = 30) were instilled intratracheally with 50 mg of quartz DQ-12 and sacrificed 15, 30, and 60 days after silica administration. Guinea pigs instilled with saline solution were used as controls. Our results showed that lung parenchymal collagenolytic activity was present in all experimental and normal guinea pigs. There were no statistical differences between silicotic and normal animals at 15 and 30 days. At 60 days, however, a significant decrease in tissue collagenolytic activity was observed in silicotic animals (161 +/- 100 vs. 400 +/- 152 units of collagenase activity; p < 0.001). In contrast, BAL collagenolytic activity was revealed only in 7 of 10 silicotic animals at 15 days and 30 days, and in 4 of 10 at 60 days. Normal guinea pigs did not exhibit BAL collagenase activity. BAL and tissue collagenase activity from each experimental animal were analyzed by straight line regression and no significant relationship was observed (r = 0.082; p = 0.87). This suggests that BAL collagenolytic activity does not reflect lung tissue collagen turnover.
 ...
PMID:Comparison between lung parenchyma and bronchoalveolar lavage collagenolytic activity. 842 65

Silicosis is characterized by pulmonary fibrotic changes which consist primarily of an increase in collagen. In this study, anticollagen antibodies in the serum of 134 silicosis patients versus 40 normal subjects were examined and their relationship with immunoglobulin, autoantibodies, and procollagen III peptide (PIIIP) was investigated by enzyme-linked immunosorbent assay (ELISA). The mean levels of anti-human type I collagen (HI) and anti-human type III collagen (HIII) antibodies were significantly higher in the silicosis patients versus the normal subjects (P < 0.001). However, no differences were observed in the mean levels of anti-human type IV collagen (HIV) antibodies in the silicosis patients versus the normal subjects. Anticollagen antibodies in the sera of silicosis patients appear to be formed at an early stage of the disease. We observed a correlation between anticollagen antibodies and immunoglobulin. There was a tendency toward high values of anticollagen antibodies in the sera of patients positive for antinuclear antibodies (ANA) and rheumatoid factor (RF), both of which are autoantibodies. However, no correlation was observed between serum PIIIP and anticollagen antibodies. These observations suggest that, in silicosis, there is a relationship between anticollagen antibodies and immunoglobulins, as well as between anticollagen antibodies and autoantibodies. Measurement of anticollagen antibodies in the sera of silicosis patients offers a useful index for evaluating the prognosis of pulmonary fibrosis and autoimmune abnormality in silicosis.
 ...
PMID:Studies on production of anticollagen antibodies in silicosis. 843 62

A better understanding is needed to explain the mechanism of therapeutic effect of combined use of tetradrine-PVNO and tetradrine-QOHP which play very important roles in treatment of silicosis. Blood prolidase (PLD), monamine oxidase (MAO) and plasminogen (PLG) in silicotic rats after treatment with tetradrine-PVNO or tetradrine-QOHP were measured. The values obtained were compared with the untreated silicotic rats. It was found that the silicotic rats that received tetradrine-PVNO showed significant increase in PLD and decrease in PLG, but no significant change in MAO. The PLD in plasma of silicotic rats that received tetradrine-QOHP were elevated significantly, but PLG and MAO did not change appreciably. These findings suggest that the combined use of tetradrine-PVNO and tetradrine-QOHP can accelerate the degradation of collagen in silicotic rats.
 ...
PMID:A biochemical study on combined treatment of experimental silicosis with tetradrine-PVNO and tetradrine-QOHP in rats. 856 27

Interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) are major proinflammatory cytokines inducing the synthesis and release of many inflammatory mediators. They are involved in immune regulation, autoimmune diseases, and inflammation. Acanthoic acid, (-)-pimara-9(11),15-dien-19-oic acid, is a pimaradiene diterpene isolated from the Korean medicinal plant, Acanthopanax koreanum. When human monocytes/macrophages stimulated with silica were treated with 0.1-10 microg/ml acanthoic acid, the production of IL-1 and TNF-alpha was inhibited up to 90%, but the production of interleukin-6 (IL-6) was not inhibited at all. At these concentrations, it had no cytotoxic effect on human monocytes/macrophages. It also suppressed the production of TNF-alpha by alveolar macrophages and lymphocytes stimulated with silica. In addition, acanthoic acid inhibited the release of superoxide anion and hydrogen peroxide from human monocytes/macrophages and neutrophils. To know the antifibrotic effects of acanthoic acid, its effects on fibroblast proliferation and collagen synthesis were tested. The proliferation of NIH3T3 cells was inhibited almost completely by the addition of the culture supernatants of human monocytes/macrophages treated with acanthoic acid, but not by the addition of acanthoic acid only. In vitro and in vivo treatment with acanthoic acid reduced collagen production by rat lung fibroblasts and lung tissue. Furthermore, acanthoic acid suppressed granuloma formation and fibrosis in the experimental silicosis. Acanthoic acid reduced serum GOT and GPT in the rats with cirrhosis induced by CCl4, and it was effective in reducing hepatic fibrosis and nodular formation. Taken together, these data indicate that acanthoic acid has a potent anti-inflammatory and antifibrosis effect by reducing IL-1 and TNF-alpha production.
 ...
PMID:Suppression of interleukin-1 and tumor necrosis factor-alpha production by acanthoic acid, (-)-pimara-9(11),15-dien-19-oic acid, and it antifibrotic effects in vivo. 866 Aug 20

Anti-bFGF serum was used to treat rabbit experimental silicosis. At 90 days, when experimental group was compared with control group, the number and size of the nodules in experimental group were much less and smaller than those in control group. Nodules in control group were mainly consist of fibroblast mixed with a small amount of collagen fiber, whereas nodules in experimental group were made up of macrophages. At 180 days, in addition to fibroblasts, there was II to III degree of collagen fiber in nodules of control group. Most of nodules in experimental group mainly contained macrophages. Fibroblasts of lung in fetal mice were cultured in vitro. The results showed that bFGF stimulated proliferation of fibroblast, whereas anti-bFGF serum inhibited fibroblast growth. It appeared that anti-bFGF serum actually blocked proliferation of fibroblast and fibrosis in rabbit experimental silicosis.
 ...
PMID:[The effect of anti basic fibroblast growth factor on the development of experimental silicosis bacillus]. 876 94

Silicosis is characterized by fibrosing nodular lesions that may eventually develop into progressive massive fibrosis (PMF). Cytokines (interleukin-1beta [IL-1beta], tumor necrosis factor-alpha [TNF-alpha] and growth factors insulin-like growth factor-1 [IGF-1] platelet-derived growth factor [PDGF]) have been implicated in the formation of these lesions. TGF-beta promotes extracellular matrix accumulation by upregulating collagen and fibronectin gene expression, and inhibits matrix degradation by decreasing secretion of proteases and increasing secretion of protease inhibitors. We hypothesized that TGF-beta is associated with matrix deposition and fibrosis in silicosis. To test this hypothesis we studied early and late nodular lesions and PMF (11 cases and two controls) with immunohistochemistry, using rabbit polyclonal antibody to the purified whole molecule of TGF-beta in Bouin's fixed lung tissue. This antibody is reactive with both intra- and extracellular forms of TGF-beta. In the control lungs, small amounts of TGF-beta were present in the bronchial epithelium, macrophages, bronchial and vascular smooth muscle, and bronchial glands. There was minimal to moderate staining in the early silicotic peribronchiolar lesions. In the nodular lesions of silicosis, central hyalinized areas contained the maximum staining for TGF-beta. Fibroblasts in the periphery of the nodular lesions were also positive. In acute silicosis, there was marked staining of hyperplastic alveolar epithelium. Macrophages were markedly positive. In the PMF lesions, large areas of scar tissue contained TGF-beta. These data suggest a major role for TGF-beta in silicosis, particularly in the formation of silicotic nodules and the development of PMF.
 ...
PMID:Transforming growth factor-beta (TGF-beta) in silicosis. 888 10


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>