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Article

Integrating signals from T-cell receptor and serum by T cells enhance translation of tumour necrosis factor-α

Citation
Buxade M, Ramirez-Alvarado M, Fernandez-Troy N, MacKenzie S, Casaroli-Marano RP, Vilella R & Espel E (2001) Integrating signals from T-cell receptor and serum by T cells enhance translation of tumour necrosis factor-α. Immunology, 102 (4), pp. 416-425. https://doi.org/10.1046/j.1365-2567.2001.01206.x

Abstract
Tumour necrosis factor-α (TNF-α) is a proinflammatory cytokine produced by several cell types, including T cells upon antigen stimulation. Its production is crucial for the development of an early defence against many pathogens, but its beneficial effects are dependent on the strength and duration of its expression. In this paper we present evidence indicating that serum increases translational efficiency of TNF-α in human peripheral blood mononuclear cells stimulated with superantigen. The increase in translation of TNF-α due to serum could be inhibited by the phosphatidylinositol (PI) 3-K inhibitors, wortmannin and LY294002, suggesting that PI 3-K is involved in the translational control of TNF-α by serum. Similarly to primary T cells, stimulation of Jurkat T cells with superantigen led to TNF-α secretion and this was up-regulated by serum. Transfection of Jurkat cells with a constitutively active form of PI 3-Kα increased the production of TNF-α in cells stimulated with superantigen. Additionally, we used the specific inhibitors targeting ERK kinase and p38 mitogen-activated protein kinase (MAPK), potentially downstream of PI 3-kinase, PD98059 and SB203580. Differently from with PI 3-K inhibitors, the accumulation of TNF-α mRNA was inhibited by PD98059 or SB203580. These results suggest that, in T cells, activation of PI 3-K is an important step in controlling TNF-α protein synthesis in response to growth factors.

Journal
Immunology: Volume 102, Issue 4

StatusPublished
Author(s)Buxade, Maria; Ramirez-Alvarado, Marina; Fernandez-Troy, Neus; MacKenzie, Simon; Casaroli-Marano, Ricardo P; Vilella, Ramon; Espel, Enric
Publication date30/04/2001
PublisherWiley-Blackwell
ISSN0019-2805
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