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J Occup Health year 2000 volume 42 number 4 page 163 - 167
Classification Originals
Title Reduced Expression of the Inhibitory Genes for Fas-Mediated Apoptosis in Silicosis Patients
Author Takemi OTSUKI1, Akiko TOMOKUNI1, Haruko SAKAGUCHI1, Fuminori HYODOH1,
Masayasu KUSAKA2 and Ayako UEKI1
Organization 1Department of Hygiene, Kawasaki Medical School,
2Department of Internal Medicine, Kusaka Hospital
Keywords Autoimmunity, Fas-mediated apoptosis, Inhibitory gene, mRNA, Silicosis
Correspondence T. Otsuki, Department of Hygiene, Kawasaki Medical School 577 Matsushima, Kurashiki, Okayama 701-0192, Japan
Abstract Reduced Expression of the Inhibitory Genes for Fas-Mediated Apoptosis in Silicosis Patients: Takemi OTSUKI, et al. Department of Hygiene, Kawasaki Medical School-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.
(J Occup Health 2000; 42: 163-168)