Tuberc Respir Dis.  1998 Aug;45(4):823-834. 10.4046/trd.1998.45.4.823.

The Production and Correlation of Silica Induced Proinflammatory Cytokines and TGF-beta from Monocytes of Balb/C Mice

• Ki SY
• Kim EY
• Kim MH
• Uh ST
• Kim YH
• Park CS
• Lee HB

• KMID: 2050098
• DOI: http://doi.org/10.4046/trd.1998.45.4.823

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.

Keyword

Silica; Fibrosis; macrophages; Proinflamatory cytokines; TGF-beta

MeSH Terms

Animals
Biological Assay
Cytokines*
Fibrosis
Horns
In Situ Hybridization
Inhalation
Interleukin-6
Lung
Macrophages
Macrophages, Alveolar
Mice*
Monocytes*
Pulmonary Fibrosis
RNA, Messenger
Silicon Dioxide*
Transforming Growth Factor beta*
Tumor Necrosis Factor-alpha
Cytokines
Interleukin-6
RNA, Messenger
Silicon Dioxide
Transforming Growth Factor beta
Tumor Necrosis Factor-alpha