Nicholas, Sally A, Sumbayev, Vadim V. (2009) The involvement of hypoxia-inducible factor 1 alpha in Toll-like receptor 7/8-mediated inflammatory response. Cell Research, 19 (8). pp. 973-983. ISSN 1001-0602. E-ISSN 1748-7838. (doi:10.1038/cr.2009.44) (Access to this publication is currently restricted. You may be able to access a copy if URLs are provided) (KAR id:45802)
PDF (Author cannot archive publisher's version/PDF)
Publisher pdf
Language: English Restricted to Repository staff only |
|
|
![]() |
Official URL: http://dx.doi.org/10.1038/cr.2009.44 |
Abstract
Toll-like receptors (TLRs) 7 and 8 are crucial in host defence against single-stranded RNA (ssRNA) viruses. Such viruses cause severe illnesses, which remain a serious medical burden in both industrialised and developing countries. TLR7/8 downstream signaling leads to a dramatic cellular stress associated with energy consumption. However, the molecular mechanisms of cell survival and adaptation to TLR7/8-induced stress, which give the cells an opportunity to initiate proper inflammatory reactions, are not clear at all. Here we report for the first time that ligand-induced activation of TLR7/8 leads to the accumulation of hypoxia-inducible factor 1 alpha (HIF-1alpha) protein in THP-1 human myeloid macrophages via redox- and reactive nitrogen species-dependent mechanisms. MAP kinases and phosphoinositol-3K are not involved in TLR7/8-mediated HIF-1alpha accumulation. Experiments with HIF-1alpha knockdown THP-1 cells have clearly demonstrated that HIF-1alpha is important for the protection of these cells against TLR7/8-induced depletion of ATP. Thus, HIF-1alpha might support both cell survival and the production of pro-inflammatory cytokines upon TLR7/8 activation.
Item Type: | Article |
---|---|
DOI/Identification number: | 10.1038/cr.2009.44 |
Uncontrolled keywords: | inflammation and innate immunity, Toll-like receptors, HIF-1 protein, apoptosis |
Subjects: | Q Science > QP Physiology (Living systems) > QP517 Biochemistry |
Divisions: | Divisions > Division of Natural Sciences > Medway School of Pharmacy |
Depositing User: | Vadim Sumbayev |
Date Deposited: | 08 Dec 2014 17:49 UTC |
Last Modified: | 16 Nov 2021 10:18 UTC |
Resource URI: | https://kar.kent.ac.uk/id/eprint/45802 (The current URI for this page, for reference purposes) |
- Export to:
- RefWorks
- EPrints3 XML
- BibTeX
- CSV
- Depositors only (login required):