Detection of alternatively spliced variant messages of Fas gene and mutational screening of Fas and Fas ligand coding regions in peripheral blood mononuclear cells derived from silicosis patients

Takemi Otsuki, Haruko Sakaguchi, Akiko Tomokuni, Takaaki Aikoh, Takakazu Matsuki, Yumika Isozaki, Fuminori Hyodoh, Yasuhiko Kawakami, Masayasu Kusaka, Shoichi Kita, Ayako Ueki

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Silicosis is clinically characterized not only by respiratory disorders but by immunological abnormalities such as the appearance of autoantibodies and complications of autoimmune diseases. Dysregulation of apoptosis, particularly in the Fas/Fas ligand (FasL) pathway, has been considered to play a role in the pathogenesis of autoimmune diseases. It has been found that serum soluble Fas (sFas) levels are elevated in silicosis patients (SIL) and the sFas message is dominantly expressed in peripheral blood mononuclear cells (PBMC) derived from these individuals. In the present study, one tried to detect alternatively spliced variant messages including typical sFas message and found four that were highly and frequently expressed, and which possess a signal peptide domain, but not transmembrane and signal transducing domains, in PBMC derived from SIL. Functional mutations were not detected in Fas and FasL genes in silicosis PBMC. Still, alternative spliced variants of the Fas gene including typical sFas message appear to play an important role in the immunological dysregulation in SIL. (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)137-143
Number of pages7
JournalImmunology Letters
Volume72
Issue number2
DOIs
StatePublished - May 1 2000

Bibliographical note

Funding Information:
This work was supported by the Japan Rheumatoid Diseases Research Foundation, Kawasaki Medical School Project Grants (9-105 and 10-105) and a Grant-in Aid for Scientific Research from the Japanese Ministry of Education, Science and Culture (1997).

Keywords

  • Alternative splicing
  • Autoimmunity
  • Fas
  • Mutation
  • Silicosis
  • Variant message

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