Role of hypoxia inducible factor-1α for interferon synthesis in mouse dendritic cells
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Regina Wobben
and
Sandra Winning
Abstract
Dendritic cells (DCs) are an important link between innate and adaptive immunity. DCs get activated in inflamed tissues where oxygen tension is usually low, which requires the transcription factor hypoxia inducible factor (HIF)-1 for cellular adaptation. To investigate whether the HIF-1 transcriptional complex plays a pivotal role in the function of DCs, we compared the effects of exogenous inflammatory stimuli and hypoxia on HIF-1α in bone marrow-derived DCs from wild type and myeloid-specific HIF-1α knock-out mice. We showed that the Toll-like receptor ligands lipopolysaccharides and cytosine-phosphatidyl-guanines significantly induce HIF-1α mRNA and protein, leading to elevated HIF-1 target gene expression of vascular endothelial growth factor. In contrast, polyinosinic:polycytidylic acid did not show comparable effects. Furthermore the potential to up-regulate inflammatory cytokines critically influences DC function. Our data demonstrate that HIF-1α protein is needed for adequate production of interferon-α and -β. In co-cultures of DCs and cytotoxic T cells, we observed that DCs lacking active HIF-1α protein induce significantly less CD278 and granzyme B mRNA in T cells. We conclude that HIF-1α plays a crucial role in DC interferon production and T cell activation, linking the innate and adaptive immune system.
©2013 by Walter de Gruyter Berlin Boston
Articles in the same Issue
- Masthead
- Masthead
- Guest Editorial
- Highlight: sensing hypoxia in the cell and the organism
- Highlight: Sensing Hypoxia in the Cell and the Organism
- Hypoxia-inducible factor prolyl 4-hydroxylases: common and specific roles
- The regulation, localization, and functions of oxygen-sensing prolyl hydroxylase PHD3
- Deciphering the emerging role of SUMO conjugation in the hypoxia-signaling cascade
- Hypoxia, the HIF pathway and neutrophilic inflammatory responses
- Hydroxylase-dependent regulation of the NF-κB pathway
- Role of hypoxia inducible factor-1α for interferon synthesis in mouse dendritic cells
- Pan-genomic binding of hypoxia-inducible transcription factors
- HIF mediated and DNA damage independent histone H2AX phosphorylation in chronic hypoxia
- Noninvasive assessment of hypoxia with 3-[18F]-fluoro-1-(2-nitro-1-imidazolyl)-2-propanol ([18F]-FMISO): a PET study in two experimental models of human glioma
- Research Articles/Short Communications
- Protein Structure and Function
- Homo- and heterotypic interactions between Pss proteins involved in the exopolysaccharide transport system in Rhizobium leguminosarum bv. trifolii
- Proteolysis
- Combination of quercetin and tannic acid in inhibiting 26S proteasome affects S5a and 20S expression, and accumulation of ubiquitin resulted in apoptosis in cancer chemoprevention
Articles in the same Issue
- Masthead
- Masthead
- Guest Editorial
- Highlight: sensing hypoxia in the cell and the organism
- Highlight: Sensing Hypoxia in the Cell and the Organism
- Hypoxia-inducible factor prolyl 4-hydroxylases: common and specific roles
- The regulation, localization, and functions of oxygen-sensing prolyl hydroxylase PHD3
- Deciphering the emerging role of SUMO conjugation in the hypoxia-signaling cascade
- Hypoxia, the HIF pathway and neutrophilic inflammatory responses
- Hydroxylase-dependent regulation of the NF-κB pathway
- Role of hypoxia inducible factor-1α for interferon synthesis in mouse dendritic cells
- Pan-genomic binding of hypoxia-inducible transcription factors
- HIF mediated and DNA damage independent histone H2AX phosphorylation in chronic hypoxia
- Noninvasive assessment of hypoxia with 3-[18F]-fluoro-1-(2-nitro-1-imidazolyl)-2-propanol ([18F]-FMISO): a PET study in two experimental models of human glioma
- Research Articles/Short Communications
- Protein Structure and Function
- Homo- and heterotypic interactions between Pss proteins involved in the exopolysaccharide transport system in Rhizobium leguminosarum bv. trifolii
- Proteolysis
- Combination of quercetin and tannic acid in inhibiting 26S proteasome affects S5a and 20S expression, and accumulation of ubiquitin resulted in apoptosis in cancer chemoprevention
