کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2794039 1155244 2015 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Knockdown of interleukin-1α does not attenuate LPS-induced production of interleukin-1β in mouse macrophages
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی علوم غدد
پیش نمایش صفحه اول مقاله
Knockdown of interleukin-1α does not attenuate LPS-induced production of interleukin-1β in mouse macrophages
چکیده انگلیسی


• IL-1β expression was decreased in TLR-4-stimulated macrophages from IL-1α-deficient mice.
• However, activation of IRF3, NFkB and p38/JNK that regulate IL-1β expression, was not reduced.
• Despite >90% knockdown of IL-1α in myeloid cells, there was no reduction in IL-1β expression levels.
• These findings do not support the previously suggested role of IL-1α in gene regulation of IL-1β.

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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cytokine - Volume 73, Issue 1, May 2015, Pages 138–143
نویسندگان
, , , , , , , , ,