Dysregulation of Fas and Related Molecules in Silicosis Patients

• TAKATA-TOMOKUNI Akiko

  Department of Hygiene, Kawasaki Medical School

• MIURA Yoshie

  Department of Hygiene, Kawasaki Medical School

• HYODOH Fuminori

  Department of Hygiene, Kawasaki Medical School

• KATSUYAMA Hironobu

  Department of Public Health, Kawasaki Medical School

• UEKI Ayako

  Department of Medical Welfare and Environmental Design, School of Medical Welfare, Kawasaki University of Medical Welfare

• OTSUKI Takemi

  Department of Hygiene, Kawasaki Medical School

Bibliographic Information

Other Title

• 珪肺症症例に検出されるＦａｓとその関連分子の異常
• ケイハイショウ ショウレイ ニ ケンシュツ サレル Fas ト ソノ カンレン ブンシ ノ イジョウ

Abstract

Silicosis patients not only suffer from respiratory disorders but also from autoimmune diseases. To clarify the mechanisms involved in the occurrence of the dysregulation of autoimmunity found in silicosis patients, we have been focusing on investigation of the Fas and Fas-related molecules in the Fas-mediated apoptotic pathway, since Fas is one of the most important molecules regulating autoimmunity in mainly T cells. Our findings showed that silicosis patients exhibited elevated serum soluble Fas levels, increased relative expression of soluble Fas and DcR 3 genes in peripheral blood mononuclear cells, other highly detectable variant messages of Fas transcripts, relatively decreased expression of several physiological inhibitors (Sentrin, I-Fline, ICAD/DFF45, and survivin), and dominancy of lower membrane Fas expressers in lymphocytes when compared with healthy volunteers. These parameters also constitute immunological factors with serum immunogulobulin G and the titer of anti-nuclear autoantibodies. In addition, anti-caspase 8 autoantibody and anti-Fas autoantibody were also detected in the serum from silicosis patients, and a functional assay showed that anti-Fas antibody stimulated Fas-mediated apoptosis. Taken together, we hypothesize that there are two subpopulations of silicosis lymphocytes. One is a long-term survival fraction including a self-recognizing fraction showing lower membrane Fas and inhibition of Fas/Fas ligand bindings in the extracellular region. The other is a fraction exhibiting apoptosis caused by silica/silicates, recruiting from bone marrow, showing higher membrane Fas and sensitive to anti-Fas autoantibody. Further investigations should be performed to confirm the effects of silica/silicates on the human immune system.

Journal

• Nippon Eiseigaku Zasshi (Japanese Journal of Hygiene)

  Nippon Eiseigaku Zasshi (Japanese Journal of Hygiene) 60 (1), 30-37, 2005

  The Japanese Society for Hygiene

Keywords

• silicosis
• autoimmunity
• Fas molecule
• apoptosis

Details

• CRID: 1390282681339359360
• NII Article ID: 10014312270
• NII Book ID: AN00185923
• DOI: 10.1265/jjh.60.30
• ISSN: 18826482
• ISSN: 00215082
• NDL BIB ID: 7245277
• PubMed: 15773295
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I7245277
• Web Site: http://www.jstage.jst.go.jp/article/jjh1946/60/1/60_1_30/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2005095690
• Text Lang: ja
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed