Soluble Fas mRNA is dominantly expressed in cases with silicosis.
Although it is well known that cases with silicosis exhibit various immunological abnormalities, the mechanisms involved in the occurrence of immuno-dysfunction or dysregulation induced by silica compounds have not yet been determined. Fas is a well-known cell surface molecule that is involved in the apoptosis pathway that belongs to the tumour necrosis factor-receptor family. Soluble Fas (sFas) is produced as an alternatively spliced product of the Fas gene and protects cells from apoptosis due to antagonization of the binding between membrane form of the Fas gene (mFas) and the Fas ligand. To determine the role of the Fas/Fas ligand system in silica-induced immunological abnormalities, we investigated Fas and Fas-ligand message expression levels using the multiplex reverse transcription-polymerase chain reaction (RT-PCR) method with peripheral blood mononuclear cells from silicosis cases with no clinical symptoms of autoimmune diseases. Although the relative expression levels of the Fas or Fas-ligand genes were not remarkably altered in these cases, we observed the sFas message was dominantly expressed compared with mFas expression. These results suggest that self-recognizing clones in cases with silicosis survive for decades, escaping the exclusion mechanisms induced by apoptosis. Then they cause the appearance of autoantibodies and the acquisition of autoimmune diseases sequentially.
Otsuki
T
T
Department of Hygiene, Kawasaki Medical School, Okayama, Japan.
Sakaguchi
H
H
Tomokuni
A
A
Aikoh
T
T
Matsuki
T
T
Kawakami
Y
Y
Kusaka
M
M
Ueki
H
H
Kita
S
S
Ueki
A
A
D000328:Adult; D000368:Aged; D053222:Fas Ligand Protein; D005260:Female; D015870:Gene Expression; D006801:Humans; D008024:Ligands; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D012595:Scleroderma, Systemic / Q000276:immunology; D012829:Silicosis / Q000276:immunology*; D012995:Solubility; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008024:Ligands; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D019014:fas Receptor