Role Of Fas/FasL Pathway Mediated Macrophage Releasing Inflammatory Cytokines In Human Silicosis | 2817
Journal of Community Medicine & Health Education
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Objective: Inflammatory cytokines play a key role in fibrosis in rodent animals. However, the mechanism of cytokine release by
the AM of silicosis patients is unclear. The present study was to investigate the role of Fas/Fas ligand (FasL) in mediating alveolar
macrophage derived inflammatory cytokines in human silicosis.
Methods: Twenty-nine silicosis patients and 6 controls with normal lung X-ray photography were selected for this study. AM
obtained from whole lung lavage fluids of all subjects treated with anti-FasL antibody or caspase-8 inhibitor for 24 hours after
purification. Six kinds of inflammatory cytokines and soluble Fas (sFas) were determined by enzyme-linked immunosorbent
assay (ELISA). Membrane-bound Fas (mFas), caspase-8, and caspase-3 were detected by Western blotting and ELISA. AM
apoptosis was detected by flow cytometry and DNA fragmentation analysis.
Results: The levels of the six kinds of cytokines in cultured AM supernatants from silicosis patients were higher than those of
controls, and increased with the progression of silicosis except TGF-β1 and IL-8. IL-1β, TNF-α, IL-8, and MCP-1 were negatively
correlated with duration of silica exposure, IL-1β and TNF-α were positively correlated with mFas, TGF-β1 was positively
correlated with mFas, caspase-8, and caspase-3 in silicosis patients. mFas, Caspase-8 and -3, TGF-β1, IL-8, MCP-1, MIP-1α, and
AM apoptosis were efficiently down-regulated by anti-FasL antibody and caspase-8 inhibitor.
Conclusions: Fas/FasL signaling serves to regulate the expression of inflammatory cytokines and to control the speed of lung
fibrosis via inhibiting AM apoptosis.
Keywords: Fas/FasL pathway; Inflammatory cytokines; Alveolar macrophages; Apoptosis; Silicosis
** This work was supported by the Natural Science Foundation of China (30671741), the Pneumoconiosis Treatment Foundation for China
Coal Miners (2005-03), and the Science and Technology Support Program of Hebei Province (09276196D).
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