| The Production and Correlation of Silica Induced Proinflammatory Cytokines and TGF-beta from Monocytes of Balb/C Mice. |
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Shin Young Ki, Eun Young Kim, Mi Ho Kim, Soo Taek Uh, Yong Hoon Kim, Choon Sik Park, Hi Bal Lee |
1Department of Internal Medicine, College of Medicine, Soonchunhyang University, Seoul, Korea.
2yonam Kidney Laboratory, Soonchunhyang University, Seoul, Korea. |
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| Abstract |
BACKGROUND
Chronic inhalation of silica induces the lung fiborsis. The alveolar macrophages ingest the inhaled silica they liberate the pro-inflammatory cytokines such as IL-i/A IL-C, TNF-a and fibrogenic cytokines, TGF-beta and PDGF. Cytokines liberated from macrophage have pivotal role in pulmonary fibrosis. There is a complex cytokine network toward fibrosis. However, the exact roles and the interaction among the proinflammatory cytokines and TGP-beta, a fibrogenic cytokine, have not been defined, yet In this study, we investigated silica induced IL-1/beta, IL-6, TNF-alpha and TGF-beta production and the effect of IL-1/beta, IL-6, TNF-alpha on the production of TGF-beta from lung macrophages of Balb/C mice. METHOD: We extracted the lung of Balb/C mice and purified monocytes by Percoll gradient method. Macrphages were stimulated by silica (SiO2) in the various concentration for 2, 4, 8, 12, and 24 bows. The supernatants were used for the measurement of protein levels by bioassay, and cells for the levels of mRNA by in situ hybridization. RESULTS: The production of IL-6 was not observed till 4 hours, and reached the peak levels at S horns after stimulation of silica. The production of TNF-alpha increased from 2 hours and reached the peak levels at 4 hours after stimulation of silica. The spontaneous TGF-beta production reached the peak levels at 24 hours. TNF-alpha upregulated the silica induced TGF-beta production Silica induced TGF-beta production was hooked by pretreated anti-TNF-alpha antibody. In situ hybridization revealed the increased positive signals at 4 hours in IL-6, at 4 hours in TNF-alpha and 12 hours in TGP-beta. CONCLUISON: The results above suggest that silica induced the sequential production of IL-6, TNF-alpha and TGF-beta from macrophages and TNF-alpha upregultaes the production of TGF-beta from silica-induced macrophages. |
| Key Words:
Silica, Fibrosis, macrophages, Proinflamatory cytokines, TGF-beta |
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