Cellular proliferation and activation of NF kappa B are induced by autocrine production of tumor necrosis factor alpha in the human T lymphoma line HuT 78

Maria A. O'Connell, Roisin Cleere, Aideen Long, Luke A. J. O'Neill, Dermot Kelleher

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Abstract

Tumor necrosis factor (TNF) is a pleiotropic cytokine which has both cytotoxic and proliferative effects. HuT 78, a T-cell line derived from a Sezary lymphoma, is resistant to the cytotoxic effects of TNF, suggesting that TNF may be a growth factor for this cell line. The aim of this study was to determine whether autocrine TNF production could function as a growth factor for HuT 78. Resting HuT 78 and K-4 cells, a protein kinase C-beta-deficient clone of HuT 78, both produced significant amounts of TNF compared with Jurkat cells. Thymidine incorporation by HuT 78 and K-4 cells was inhibited by 90.5 and 73.2%, respectively, with addition of a neutralizing monoclonal antibody to TNF alpha, suggesting that TNF is an autocrine growth factor for these cells. HuT 78 and K-4 cells also expressed high levels of constitutively active NF kappa B, unlike Jurkat cells, which expressed high levels only upon activation with TNF or phorbol 12-myristate 13-acetate. p50 was the major component in the NF kappa B complexes in HuT 78 and K-4 cells. Anti-TNF alpha antibody dramatically decreased levels of NF kappa B in both HuT 78 and K-4 cells. As the TNF gene has an NF kappa B binding motif, an autocrine loop involving TNF induction of NF kappa B is therefore likely in these cells. These findings in a neoplastic T-cell line suggest that therapy directed against TNF could be effective in a subset of T-cell lymphomas.
Original languageEnglish
Pages (from-to)7399-7404
Number of pages6
JournalJournal of Biological Chemistry
Volume270
Issue number13
DOIs
Publication statusPublished - 31 Mar 1995

Keywords

  • Antibodies, Monoclonal
  • Base Sequence
  • Carrier Proteins
  • Cell Division
  • Cell Line
  • Clone Cells
  • Consensus Sequence
  • Humans
  • Interleukin-1
  • Interleukin-2
  • Kinetics
  • Lymphoma, T-Cell
  • Membrane Proteins
  • Molecular Sequence Data
  • NF-kappa B
  • Oligodeoxyribonucleotides
  • Organic Cation Transporter 1
  • Recombinant Proteins
  • Subcellular Fractions
  • Tetradecanoylphorbol Acetate
  • Thymidine
  • Time Factors
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha

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