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© Fabrice Chrétien with Ultrapole, colorized by Jean-Marc Panaud
Cellule souche (en jaune) de muscle squelettique partiellement recouverte par la membrane basale, migrant sur une fibre musculaire (en bleu).
Publication : International immunology

IL-2-induced tumor necrosis factor (TNF)-beta expression: further analysis in the IL-2 knockout model, and comparison with TNF-alpha, lymphotoxin-beta, TNFR1 and TNFR2 modulation

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in International immunology - 01 Feb 2001

Reddy J, Chastagner P, Fiette L, Liu X, Thèze J

Link to Pubmed [PMID] – 11157847

Int. Immunol. 2001 Feb;13(2):135-47

IL-2 induces the stimulation of inflammatory and immune reactions, and the apoptosis of antigen-activated cells. However, the molecular basis of these pleiotropic functions is largely unknown. We have previously reported that IL-2 induces genes involved in cytoskeleton organization, oncogene regulation and transcriptional control. In an IL-2-dependent cell line, we have also shown that IL-2 induces tumor necrosis factor (TNF)-beta mRNA through the Jak-STAT pathway. Here, we first demonstrate in vitro that IL-2 induces mature and partially spliced TNF-beta mRNA in the splenocytes and lymph node cells of both IL-2(-/-) and IL-2(+/-) mice. Under the same experimental conditions, IL-2 is seen to induce TNF-alpha mRNA. mRNA expression is followed by semiquantitative RT-PCR and this analysis is then extended in vivo by studying different lymphoid organs from IL-2(-/-)animals. Strikingly, the expression of TNF-beta mRNA is noted to be extremely low in the spleens and lymph nodes of IL-2(-/-) mice. Similarly, TNF-alpha, lymphotoxin (LT)-beta, TNFR1 and TNFR2 mRNA levels are also low in the spleens of IL-2(-/-) animals, whereas IFN-gamma and IL-4 mRNA levels remain unaffected in these animals. The experimental values are significantly different (P < or = 0.05) from those of control IL-2(+/-) animals. Western blot analysis of TNF-alpha expression confirmed and extended the results at the protein level. For the first time, we demonstrate that IL-2 directly or indirectly regulates genes of the TNF-TNFR family in secondary lymphoid organs. Furthermore, IL-2(-/-) animals in which thymopoiesis is unaffected show normal expression of these genes. Altogether, our data further define the pleiotropic effects of IL-2 at the molecular level.

http://www.ncbi.nlm.nih.gov/pubmed/11157847