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Crosstalk between toll-like receptors and hypoxia-dependent pathways in health and disease

Bianca Crifo, Cormac T Taylor
DOI: 10.1097/JIM.0000000000000228 Published 28 January 2016
Bianca Crifo
School of Medicine and Medical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin, Ireland
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Cormac T Taylor
School of Medicine and Medical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin, Ireland
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    Figure 1

    Toll-like receptors in humans. Distinct TLRs discriminate between different microbial patterns. The extracellular LRR domain of each TLR is involved in recognizing its specific microbial ligand, whereas the intracellular TIR domain serves to assemble adaptor protein complexes. All TLRs, with the exception of TLR3, use MyD88 to activate downstream signaling pathways. In some cases (eg, TLR2/6, TLR2/1, and TLR4), the MAL adaptor protein mediates the interaction between TLRs and MyD88. TLR3 and TLR4 use TRIF to transmit the downstream signal. In addition, TLR4 recruits TRAM as bridge. TLR4 is the only receptor that use all 4 adaptors.

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    Figure 2

    HIF-pathway in normoxia and hypoxia. In the presence of molecular oxygen, PHDs hydroxylate HIF-α promotes its interaction with the von Hippel-Lindau E3 ligase complex. This complex mediates ubiquitination and the proteasomal degradation of HIF-α. Factor inhibiting HIF-dependent ASN hydroxylation prevents interactions between HIF-α subunitsand CBP/p300 and thus prevents transactivation. In hypoxia, the HIF hydroxylases are inactivated and therefore HIF-α can heterodimerize with HIF-1β, translocate to the nucleus, and interact with transcriptional coactivators (eg, CPB/p300) to mediate the transcription of genes involved in adaptation.

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Vol 64 Issue 2 Table of Contents
Journal of Investigative Medicine: 64 (2)
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Crosstalk between toll-like receptors and hypoxia-dependent pathways in health and disease
Bianca Crifo, Cormac T Taylor
Journal of Investigative Medicine Feb 2016, 64 (2) 369-375; DOI: 10.1097/JIM.0000000000000228

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Crosstalk between toll-like receptors and hypoxia-dependent pathways in health and disease
Bianca Crifo, Cormac T Taylor
Journal of Investigative Medicine Feb 2016, 64 (2) 369-375; DOI: 10.1097/JIM.0000000000000228
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Crosstalk between toll-like receptors and hypoxia-dependent pathways in health and disease
Bianca Crifo, Cormac T Taylor
Journal of Investigative Medicine Feb 2016, 64 (2) 369-375; DOI: 10.1097/JIM.0000000000000228
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  • Article
    • Abstract
    • Toll-Like Receptors
    • Toll-Like Receptor Localization and Pathogen-Associated Molecular Pattern Ligands
    • Toll-Like Receptor Structure and Complexes
    • NF-κB Signaling
    • Hypoxia and the Hypoxia-Inducible Factor Pathway
    • Crosstalk Between TLR and HIF Pathways
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