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

The type II pneumocyte changes in silicosis are characterized by hyperplasic and hypertrophic epithelial cells, and increased surfactant phospholipids in the bronchoalveolar lavage fluids (BALF). To assess the proliferative activity of alveolar lining fluids, BALF were applied on type II cell cultures. The growth-promoting activity was studied by tritiated thymidine incorporation for 24 h, and the cell number was measured by an electronic counting after a 48-h exposure time. Human BALF from 3 subsets of workers exposed to silica, staged according to ILO classification (silica exposed-workers without disease: hSWD n = 6; workers with simple silicosis: hSS n = 7; workers with confluent silicosis: hCS n = 5), were compared to healthy volunteers (hC n = 6). Sheep BALF from our model of silicosis and control animals (sS and sC) were studied at months 0, 6, and 24 of exposure. A clear enhancement was found in type II cell DNA synthesis under the effect of either normal and silicotic human or sheep BALF, in comparison to the negative control (p less than .05). In addition hSWD and hSS BALF as sS BALF at 20% dilution (peak activity) were significantly more stimulating than the normal alveolar fluids from the same species (p less than .05). The highest sheep BALF stimulatory activity was found at month 6 (170% of increase vs control, p less than .05) and clearly correlated with the high cellularity of BALF. The thymidine incorporation was supported by changes in cell counts. Sheep silicotic BALF run through G50 columns identified at least 3 molecular weight (MW) areas of mitogenic activity between 30 and 5 kDa. Biochemical characteristics of growth factors in the above MW range (PDGF, FGF, TGF alpha, EGF) were tested. Increased mitogenic activity of type II cells eluted from heparin sepharose columns loaded with silicotic sheep BALF, at 0.5 and 1 M NaCl, corresponded to the removal areas of PDGF- and acidic FGF-like heparin-binding molecules. The high proliferative activity on type II cells of the latter two molecules, alone or in combination with other growth factors, was demonstrated in vitro (greater than 9 x control). In conclusion, a stimulatory activity for type II cell growth was found in the normal human and sheep alveolar lining fluid. This activity was clearly enhanced in the early stages of human and sheep silicosis. The BALF type II cell growth factors had biochemical characteristics consistent with the PDGF- and FGF-like molecules.
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PMID:Silica-exposed lung fluids have a proliferative activity for type II epithelial cells: a study on human and sheep alveolar fluids. 132 31

Tetrandrine, an herbal drug, has been employed in China to treat pulmonary fibrosis. To date, the mechanisms governing the antifibrotic action of tetrandrine are unknown. The present study employs a fibroblast mitogenic assay to determine whether tetrandrine directly inhibits the ability of fibroblasts to respond to stimulation by growth factors. The data indicate that tetrandrine blocks proliferation and the incorporation of tritiated thymidine into DNA by fibroblasts stimulated with human serum, PDGF plus plasma, FGF plus plasma, or TNF plus plasma. Since tetrandrine inhibits the response to a variety of growth factors, its action does not appear to involve the blockade of a specific stimulatory receptor. Tetrandrine is effective in inhibiting thymidine incorporation when added up to 6 hr after stimulation of quiescent cells, suggesting either that tetrandrine does not block the attainment of competence by fibroblasts or that its activity is not limited to blocking the attainment of competence by these cells. Growth factor-induced mitogenesis is also inhibited by nitrendipine, a calcium channel blocker, and by cytochalasin B, a microfilament blocker. However, tetrandrine treatment of fibroblasts neither results in the changes of morphology seen with cytochalasin B nor is limited to the early events of stimulus-response coupling. Therefore, the mechanism of action for tetrandrine is not identical to that for either cytochalasin B or nitrendipine. In summary, these results suggest that the antifibrotic action of tetrandrine may be mediated in part by direct inhibition of fibroblast proliferation normally associated with the development and progression of silicosis.
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PMID:Inhibition of proliferative activity of pulmonary fibroblasts by tetrandrine. 810 60

The proliferation of lung epithelial cells is a prominent feature of lung tissue response following silica-induced lung injury and alveolar macrophages are recognized as a major contributing cell to the lung inflammatory processes. In previous studies, a growth-promoting activity for fetal rat lung epithelial cells was observed in silicotic alveolar fluids and in supernatants from in vitro and in vivo silica-exposed alveolar macrophages. In the present work, the biological and physicochemical properties of the macrophage-derived growth-promoting activity for fetal lung epithelial cells were explored. Four peaks of growth-promoting activity for lung epithelial cells ranging from 32 to 7 kDa were found in both in vitro and in vivo silica-exposed macrophage supernatants. The investigations were coupled with biochemical treatments of the mitogenic peaks and blocking antibodies or antisera were used to specify further the nature of the proliferative activities. Among the established growth factors, alveolar macrophage-derived growth fractions had characteristics consistent with platelet-derived growth factor-, insulin-like growth factor 1-, and fibroblast growth factor-like molecules. The cytokine production following in vitro exposure, which reflects very early events in the pathogenesis of silicosis, was more strongly related to the high-molecular-weight PDGF-like molecules, whereas the cytokine production following in vivo exposure, which reflects later events in the pathogenesis of silicosis, was more influenced by intermediate-molecular-weight FGF- and IGF-like molecules.
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PMID:Partial characterization of the proliferative activity for fetal lung epithelial cells produced by silica-exposed alveolar macrophages. 818 35