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

Jayagopala Reddy, Patricia Chastagner, Laurence Fiette, Xinyuan Liu, Jacques Thèze

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

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)-β mRNA through the Jak-STAT pathway. Here, we first demonstrate in vitro that IL-2 induces mature and partially spliced TNF-β 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-α 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-β mRNA is noted to be extremely low in the spleens and lymph nodes of IL-2-/- mice. Similarly, TNF-α, lymphotoxin (LT)-β, TNFR1 and TNFR2 mRNA levels are also low in the spleens of IL-2-/- animals, whereas IFN-γ and IL-4 mRNA levels remain unaffected in these animals. The experimental values are significantly different (P ≤ 0.05) from those of control IL-2+/- animals. Western blot analysis of TNF-α 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.

Original languageEnglish (US)
Pages (from-to)135-147
Number of pages13
JournalInternational Immunology
Volume13
Issue number2
DOIs
StatePublished - 2001
Externally publishedYes

Keywords

  • Cytokine receptors
  • Cytokines
  • Knockout

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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