Knockdown of interleukin-1α does not attenuate LPS-induced production of interleukin-1β in mouse macrophages

Tal Almog, Michal Kandel-Kfir, Aviv Shaish, Moshe Dissen, Gadi Shlomai, Elena Voronov, Ron N. Apte, Dror Harats, Yehuda Kamari

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


IL-1α and IL-1β are synthesized as 31. kDa cell-associated precursors following TLR-4 stimulation, but their processing to the mature form and secretion require a second intracellular stimulus. The unique localization of the precursor of IL-1α (pro-IL-1α) to the nucleus suggested a role in transcriptional regulation of inflammatory cytokines. We explored the hypothesis that pro-IL-1α is involved in regulation of IL-1β expression following TLR-4 stimulation. IL-1β mRNA and protein levels were specifically decreased in macrophages from IL-1α-deficient mice following TLR-1/2, TLR-4 or TLR-9 stimulation, supporting the hypothesis. However, activation of the main upstream regulators of IL-1β expression, IRF3, NFkB and p38/JNK, were not reduced in macrophages from IL-1α-deficient mice. In order to assess the specific role of IL-1α in macrophages, we generated mice with myeloid cell deficiency of IL-1α (LyzMCre-loxp). Despite over 90% knockdown of IL-1α, TLR-4 stimulated macrophages from LyzMCre-loxp mice did not produce lower levels of IL-1β compared to IL-1α-loxp-flanked mice. In order to overcome the possibility that effects are caused by the incomplete deficiency of IL-1α, we generated new whole-body IL-1α knockout mice (GeneralCre-IL-1α) and the findings were similar to myeloid cell-deficient IL-1α. Collectively, our findings do not support the previously suggested role of nuclear IL-1α in gene regulation of IL-1β. Rather, they suggest that IL-1α acts mainly as an alarmin that is sequestered in the nucleus following stimulation with TLR-4.

Original languageEnglish
Pages (from-to)138-143
Number of pages6
Issue number1
StatePublished - 1 May 2015


  • IL-1α
  • IL-1β
  • LyzMCre
  • Macrophages
  • TLR-4

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Molecular Biology
  • Hematology


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