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Increase in expression levels of interferon-inducible genes in senescent human diploid fibroblasts and in SV40-transformed human fibroblasts with extended lifespan. 1995

H Tahara, and K Kamada, and E Sato, and N Tsuyama, and J K Kim, and E Hara, and K Oda, and T Ide
Department of Cellular and Molecular Biology, Hiroshima University School of Medicine, Japan.

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.

UI MeSH Term Description Entries
D007371 Interferon-gamma The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES. Interferon Type II,Interferon, Immune,gamma-Interferon,Interferon, gamma,Type II Interferon,Immune Interferon,Interferon, Type II
D007372 Interferons Proteins secreted by vertebrate cells in response to a wide variety of inducers. They confer resistance against many different viruses, inhibit proliferation of normal and malignant cells, impede multiplication of intracellular parasites, enhance macrophage and granulocyte phagocytosis, augment natural killer cell activity, and show several other immunomodulatory functions. Interferon
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002461 Cell Line, Transformed Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals. Transformed Cell Line,Cell Lines, Transformed,Transformed Cell Lines
D002471 Cell Transformation, Neoplastic Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill. Neoplastic Transformation, Cell,Neoplastic Cell Transformation,Transformation, Neoplastic Cell,Tumorigenic Transformation,Cell Neoplastic Transformation,Cell Neoplastic Transformations,Cell Transformations, Neoplastic,Neoplastic Cell Transformations,Neoplastic Transformations, Cell,Transformation, Cell Neoplastic,Transformation, Tumorigenic,Transformations, Cell Neoplastic,Transformations, Neoplastic Cell,Transformations, Tumorigenic,Tumorigenic Transformations
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D005347 Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Fibroblast
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013539 Simian virus 40 A species of POLYOMAVIRUS originally isolated from Rhesus monkey kidney tissue. It produces malignancy in human and newborn hamster kidney cell cultures. SV40 Virus,Vacuolating Agent,Polyomavirus macacae,SV 40 Virus,SV 40 Viruses,SV40 Viruses,Vacuolating Agents

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