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The involvement of hypoxia-inducible factor 1 alpha in Toll-like receptor 7/8-mediated inflammatory response

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)

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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: Faculties > Sciences > Medway School of Pharmacy
Depositing User: Vadim Sumbayev
Date Deposited: 08 Dec 2014 17:49 UTC
Last Modified: 29 May 2019 13:50 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/45802 (The current URI for this page, for reference purposes)
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