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

O'Connell, M A, Cleere, R, Long, A, O'Neill, L A and Kelleher, D (1995) 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. Journal of Biological Chemistry, 270 (13). pp. 7399-404. ISSN 0021-9258

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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.

Item Type: Article
Uncontrolled 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
Faculty \ School: Faculty of Science > School of Pharmacy
Depositing User: Pure Connector
Date Deposited: 11 Jun 2014 14:08
Last Modified: 05 Nov 2018 16:31
URI: https://ueaeprints.uea.ac.uk/id/eprint/48273
DOI:

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