期刊
CELL RESEARCH
卷 19, 期 8, 页码 973-983出版社
INST BIOCHEMISTRY & CELL BIOLOGY
DOI: 10.1038/cr.2009.44
关键词
inflammation and innate immunity; Toll-like receptors; HIF-1 protein; apoptosis
类别
资金
- Medway School of Pharmacy, University of Kent (UK)
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-1 alpha) 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-1 alpha accumulation. Experiments with HIF-1 alpha knockdown THP-1 cells have clearly demonstrated that HIF-1 alpha is important for the protection of these cells against TLR7/8-induced depletion of ATP. Thus, HIF-1 alpha might support both cell survival and the production of pro-inflammatory cytokines upon TLR7/8 activation.
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