Increase in expression levels of interferon-inducible genes in senescent human diploid fibroblasts and in SV40-transformed human fibroblasts with extended lifespan

Oncogene. 1995 Sep 21;11(6):1125-32.

Abstract

The normal human fibroblast line, TIG-3 which senesces at around 80 population doubling levels (PDLs), expressed interferon (IFN)-inducible genes such as 6-16, 2', 5'-oligoadenylate synthetase (2,5-A) and HLA B7 near the end of the proliferative lifespan. Other normal fibroblast line such as MRC-5 also expressed IFN-inducible genes when senesced. Clones transformed with SV40 T-antigen, which extended their proliferative lifespan by about 20-30 PDLs, also expressed IFN-inducible genes during their extended life. Anti-IFN-beta antibodies added in culture medium repressed the expression of IFN-inducible gene in both normal senescent and life-extended SV40-transformed cells. IFN-beta repressed DNA synthesis in normal TIG-3 and induced IFN-inducible genes in both normal and SV40-transformed TIG-3. Conditioned medium recovered from life-extended SV40-transformed cells contained IFN-beta, but not IFN-alpha, IFN-gamma or TNF-alpha and possessed an activity that inhibited DNA synthesis of young TIG-3. Addition of anti-IFN-beta antibodies into the medium enhanced the serum-induced DNA synthesis of near senescent (91% lifespan completed) TIG-3, while it neither induced DNA synthesis in fully senescent TIG-3 nor extended the proliferative lifespan of TIG-3. These results suggest that normal and SV40-transformed human fibroblasts increase expression of IFN-beta with increasing proliferative age especially near the end of their lifespan resulting in induction of IFN-inducible genes and possibly in growth repression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Line, Transformed
  • Cell Transformation, Neoplastic*
  • Cellular Senescence*
  • DNA / biosynthesis
  • Fibroblasts
  • Gene Expression Regulation*
  • Humans
  • Interferon-gamma / biosynthesis
  • Interferons / pharmacology*
  • Simian virus 40 / genetics

Substances

  • Interferon-gamma
  • DNA
  • Interferons