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Autoproliferation of Fibroblast by Exposure to Crystalline Silica - Evaluation by H2O2 and PDGF-AA and TGF beta
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Byoung Young Ahn, Kyoung Ah Kim, Je Hyeok Mun, Jin Sook Jeong, Eun Kyung Kim, Young Lim
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Korean Journal of Occupational and Environmental Medicine 2000;12(2):209-217. Published online June 30, 2000
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DOI: https://doi.org/10.35371/kjoem.2000.12.2.209
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 Abstract
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- OBJECTIVES
The aim of this study is to find out the activity of autoproliferation of ratfibroblast exposed to crystalline silica and the role of mediators secreted from rat fibroblast.
METHODS
The effect of alpha-quartz on production of growth factor (platelet-derived growth factor-AA and transforming growth factor beta)from rat fibroblasts were evaluated by ELISA and immunocytochemical analysis.
Gene expression of these growth factors in rat fibrobast exposed to crystalline silica was evaluated by RT-PCR.
Furthermore, fibroblast proliferation by culture supernatant of rat fibroblast was assayed by the neutral red test.
RESULTS
The amounts of H2O2 and growth factors synthesized in rat fibroblasts were significantly increased by the stimulation of crystalline silica(alpha-quartz), which showed the dose-dependent manner to the concentration of alpha-quartz with the maximum response at the dosage of 100 microgram/cm2. The result of RT-PCR demonstrated that alpha-quartz induced gene expression of PDGF-AA and TGFbeta in rat fibroblast. We also found that supernatant of alpha-quartz-cocultured rat fibroblast induced a significant proliferation of fibroblast.
CONCLUSION
Crystalline silica directly induce functional change in fibroblast such as increased release of reactive oxygen species and growth factors. The products of these functional change promote fibroblast proliferation via autocrine loop.
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Reactive Oxygen Species Generation of Refractory Ceramic Fiber and Rock Wool-Induced Alveolar Macrophage and Associated Signal Transduction Pathway
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Eun Kyung Kim, Kyoung Ah Kim, Young Lim, Kyung Sook Yang, Hyun Sook Oh, Kweon Haeng Lee
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Korean Journal of Occupational and Environmental Medicine 1999;11(4):527-533. Published online December 31, 1999
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DOI: https://doi.org/10.35371/kjoem.1999.11.4.527
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Abstract
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- OBJECTIVES
It is known that the high fibrogenecity of particles is connected with their cytotoxicity for macrophages. Although the molecular mechanism leading to fiber-induced fiber-induced cytotoxicity is still not clear, several mechanism have been suggested. The release of reactive oxygen species (ROS) from activated alveolar macrophages (AM) by dust have been suggested as a possible mechanism of particle-induced cell damage. But the mechanism which man-made vitreous fiber (MMVF) induces the production of ROS in AM is still not clear. In this study, we evaluated the relationship between ROS production and lactate dehydrogenase (LDH) release from alveolar treated with refractory ceramic fiber (RF2) or rock wool (RW1) and signal transduction path-way of ROS production in RF2 or RW1 exposed AM.
METHODS
We investigated LDH release from MMVF-stimulated AM for index of cytotoxicity. To determine what kind of signal transduction pathways are involved in MMVF-stimulated ROS generation, we used some drugs which have an effect on the signal transduction pathway.
RESULTS
RF2 and RW1 induced increase of LDH release with dose-dependent manner with RF2 having greater effect than RW1. There was a dose-dependent increase in the production of ROS by RF2 or RW1. At all level of concentration,. RF2 induced more ROS production than RW1. Inhibitors of PKC (bisindolylmaleimide), PLC (U73122 and neomycine) and PTK (genistein and erbstatin) suppressed RF2 or RW1-induced ROS production.
CONCLUSION
There was significant correlation between LDH release and ROS production from AM treated with RF2 or RW1. RF2 and RW1 induced ROS generation through protein kinase C (PKC), phospholipase C (PLC) and protein tyrosin kinase (PTK) pathways.
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Effect of Desferrioxamine on Silica-Induced Cytotoxicity of A549 and Fibroblast Proliferation
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Kyoung Ah Kim, Eun Kyung Kim, Ji Hong Kim, Young Lim
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Korean Journal of Occupational and Environmental Medicine 1999;11(2):127-136. Published online June 30, 1999
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DOI: https://doi.org/10.35371/kjoem.1999.11.2.127
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Abstract
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- The inhalation of crystalline silica results in the production of reactive oxygen species(ROS). Among these ROS, hydroxyl radical( OH) is believed to be the most reactive one. OH is generated in reaction between superoxide and hydrogen peroxide catalyzed by transition metal, especially iron. Therefore iron should be important in the bioactivity of crystalline silica. Desferrioxamine, a iron chelator, may be protective in silica-induced pulmonary reaction. To test this assumption we investigated the protective effect of desferrioxamine on lipid peroxidation of cell membrane, cytotoxicity, production of proinflammatory and chemotactic cytokine and fibroblast proliferation by crystalline silica in vitro model. The results were as follows: 1. Fenton activity of silica and asbestos was significantly higher than that of control. Fenton activity in crocidolite was higher than silica at the same dose. This result correlated with iron content of dust. Fenton activity of silica and crocidolite was decreased by preincubation of silica with desferrioxamine. 2. Silica induced a dose-dependent increase of MIDA concentration in lung epithelial cell lysate dose dependently. Marked decrease of MDA was observed in desferrioxaminetreated silica group compared with untreated group. 3. As concentration of stimulated silica, silica?induced cytotoxicity was increased. There was significant decrease of cytotoxicity in desferrioxamine?treated silica group compared with untreated group. 4. a-quartz augmented the production of TNF-a and IL-8 from A549 cell. While desferrioxa-mine suppressed the release of cytokines. 5. Supernatant of silica-cocultured A549 cell induced a significant proliferation of fibroblast, which desferrioxaime blocked this proliferation. From these result, we concluded that desferrioxamine has a protective effect on silica induced pulmonary reaction.
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