کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2832637 1163841 2008 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
HIF-1α protein is an essential factor for protection of myeloid cells against LPS-induced depletion of ATP and apoptosis that supports Toll-like receptor 4-mediated production of IL-6
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی مولکولی
پیش نمایش صفحه اول مقاله
HIF-1α protein is an essential factor for protection of myeloid cells against LPS-induced depletion of ATP and apoptosis that supports Toll-like receptor 4-mediated production of IL-6
چکیده انگلیسی

Sepsis is the leading cause of death in intensive care units, which reflects detrimental host response to infection where lipopolysaccharide (LPS) shared by Gram-negative bacteria acts as a potent activator of immune cells via Toll-like receptor 4 (TLR4). Recently it was found that TLR4 downstream signalling leads to the accumulation of hypoxia-inducible factor 1 alpha (HIF-1α), which is important for TLR4-dependent expression of pro-inflammatory cytokines, however, basic biochemical mechanisms of involvement of this protein in TLR4 downstream signalling remains unclear. Here we found that knockdown of the expression of HIF-1α protein by siRNA led to the depletion of ATP, which corresponded to the constant increase in the activity of apoptosis signal-regulating kinase 1 (ASK1) and therefore apoptosis as estimated based on the increase in the activity of caspase 3. On the other hand, LPS-dependent production of IL-6 was attenuated. Treatment of HIF-1α knockdown cells with extracellular ATP in combination with LPS preserved the IL-6 expression but not the activity of ASK1 on the level observed in LPS-stimulated control cells. We therefore suggested that HIF-1α protein supports LPS-dependent expression of IL-6 by preventing depletion of ATP. On the other hand HIF-1α protein is selectively required for down-regulation of ASK1 activated during LPS-induced TLR4 downstream signalling.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Immunology - Volume 45, Issue 11, June 2008, Pages 3045–3049
نویسندگان
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