Over-expression of the decoy receptor 3 (DcR3) gene in peripheral blood mononuclear cells (PBMC) derived from silicosis patients

Dysregulation of apoptosis, particularly in the Fas/Fas ligand (FasL) pathw ay, is considered to be involved in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE). Recently, a soluble decoy rece ptor, termed decoy receptor 3 (DcR3), that binds FasL and inhibits FasL-ind uced apoptosis, has been identified. Silicosis is clinically characterized not only by respiratory disorders but by immunological abnormalities. We ha ve found that serum soluble Fas (sFas) levels are elevated in silicosis pat ients and that sFas message is dominantly expressed in PBMC derived from th ese patients. This study examined DcR3 gene expression in PBMC derived from patients with silicosis, SLE, or progressive systemic sclerosis (PSS), and compared it with that in healthy volunteers (HV). The relative expression level of the DcR3 gene was examined in PBMC derived from 37 patients with s ilicosis without clinical symptoms of autoimmune disease, nine patients wit h SLE, 12 patients with PSS, and 28 HV using the semiquantitative multiplex -reverse transcriptase-polymerase chain reaction (MP-RT-PCR). The correlati on between the relative expression level of the DcR3 gene and multiple clin ical parameters for respiratory disorders and immunological abnormalities i n individuals with silicosis was analysed. The DcR3 gene was significantly over-expressed in cases of silicosis or SLE when compared with HV. In addit ion, the DcR3 relative expression level was positively correlated with the serum sFas level in silicosis patients. It is unclear, however, whether ove r-expression of the DcR3 gene in silicosis is caused by chronic silica expo sure, merely accompanies the alteration in Fas-related molecules, or preced es the clinical onset of autoimmune abnormalities. It will be necessary to study these patients further, establish an in vitro model of human T cells exposed recurrently to silica compounds, and resolve whether the increase i n DcR3 mRNA expression is a cause or consequence of disease.