Reduced expression of the inhibitory genes for Fas-mediated apoptosis in silicosis patients

Silicosis cases are characterized not only by respiratory disorders but by various immunological abnormalities, but the cellular biological effects of silica compounds on human lymphocytes have not been well investigated. Our previous studies revealed high serum soluble Fas (sFas) levels in silicosis patients without any clinical symptoms of autoimmune disease and the dominant expression of sFas mRNA in peripheral blood mononuclear cells (PBMC) derived from these patients. These observations indicate that dysregulation of the Fas gene may play an important role in the pathogenesis of the immunological abnormalities found in silicosis patients. Recently several molecules with inhibitory or regulatory effects on Fas-mediated apoptosis have been identified and their cellular biological roles investigated. We examined the mRNA expression of inhibitory genes (TOSO, sentrin, and cFLIP), regulatory genes (CPAN and DFF45), and caspases (caspase-1, -3, and -8) in PBMC derived from silicosis patients. The results showed a reduced expression of sentrin, cFLIP and DFF45 and an overexpression of caspase-1. Nevertheless, considering the remarkable dominant expression of sFas in silicosis, the dysregulation of inhibitory genes and caspase-1 may be evidence of a Fas-mediated apoptotic pathway activated via the remaining membrane Fas molecules in the PBMC of silicosis patients.