Toll-like receptor activation and hypoxia use distinct signaling pathways to stabilize hypoxia-inducible factor 1α (HIF1A) and result in differential HIF1A-dependent gene expression

Autor: Joachim Gläsner, Jonathan Jantsch, Kirstin Castiglione, Ulrike Schleicher, Markus Schnare, Carsten Willam, David R. Mole, Melanie Wiese, Kai-Uwe Eckardt, Sophie Kolbe, Roland Lang, Johannes Schödel, Christian Bogdan, Michael Hensel
Rok vydání: 2011
Předmět:
Lipopolysaccharides
Chromatin Immunoprecipitation
Cellular differentiation
Blotting
Western
Immunology
Biology
Proinflammatory cytokine
Mice
03 medical and health sciences
0302 clinical medicine
medicine
Animals
Immunology and Allergy
RNA
Messenger
Hypoxia
Transcription factor
Cell Proliferation
Oligonucleotide Array Sequence Analysis
030304 developmental biology
Mice
Knockout
0303 health sciences
Reverse Transcriptase Polymerase Chain Reaction
Gene Expression Profiling
NF-kappa B
Cell Differentiation
Dendritic Cells
Cell Biology
Hypoxia (medical)
Hypoxia-Inducible Factor 1
alpha Subunit
Cell biology
Mice
Inbred C57BL
Toll-Like Receptor 4
Adaptor Proteins
Vesicular Transport
HIF1A
Hypoxia-inducible factors
TRIF
030220 oncology & carcinogenesis
Myeloid Differentiation Factor 88
medicine.symptom
Signal transduction
Biomarkers
Signal Transduction
Zdroj: Europe PubMed Central
ISSN: 1938-3673
0741-5400
Popis: HIF1A is a transcription factor that plays a central role for the adaptation to tissue hypoxia and for the inflammatory response of myeloid cells, including DCs. HIF1A is stabilized by hypoxia but also by TLR ligands under normoxic conditions. The underlying signaling events leading to the accumulation of HIF1A in the presence of oxygen are still poorly understood. Here, we show that in contrast to hypoxic stabilization of HIF1A, normoxic, TLR-mediated HIF1A accumulation in DCs follows a different pathway that predominantly requires MYD88-dependent NF-κB activity. The TLR-induced HIF1A controls a subset of proinflammatory genes that are insufficiently induced following hypoxia-mediated HIF1A induction. Thus, TLR activation and hypoxia stabilize HIF1A via distinct signaling pathways, resulting in differential HIF1A-dependent gene expression.
Databáze: OpenAIRE
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