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https://hdl.handle.net/2440/65651
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Type: | Journal article |
Title: | The involvement of sphingosine kinase 1 in LPS-induced Toll-like receptor 4-mediated accumulation of HIF-1a protein, activation of ASK1 and production of the pro-inflammatory cytokine IL-6 |
Author: | Pchejetski, D. Nunes, J. Coughlan, K. Lall, H. Pitson, S. Waxman, J. Sumbayev, V. |
Citation: | Immunology and Cell Biology, 2011; 89(2):268-274 |
Publisher: | Blackwell Publishing Asia |
Issue Date: | 2011 |
ISSN: | 0818-9641 1440-1711 |
Statement of Responsibility: | Dmitri Pchejetski, Joao Nunes, Karen Coughlan, Harjinder Lall, Stuart M Pitson, Jonathan Waxman and Vadim V Sumbayev |
Abstract: | Toll-like receptors (TLRs) lie in the core of resistance to infectious diseases allowing host immune cells to specifically detect pathogens by recognising their specific molecular patterns. Cell membrane-associated TLR4 (recognises lipopolysaccharide (LPS) of Gram-negative bacteria) and endosomal TLR7/8 (recognise viral single-stranded RNA) are known to activate hypoxia inducible factor-1α (HIF-1α) protein (necessary for cellular adaptation to the inflammatory stress) via redox-dependent mechanism. TLR4 triggers the cross talk between HIF-1α and apoptosis signal-regulating kinase 1 (ASK1), whereas TLR7/8 activates HIF-1α in the ASK1-independent manner. Here, we report that in THP-1 and RAW264.7 macrophages, ligand-induced activation of the TLR4 but not TLR7/8 induces activation and transcriptional upregulation of sphingosine kinase 1 (SphK1) in extracellular signal-regulating kinase and phospholipase C-1γ/PI3 kinase-dependent manner. TLR4-mediated SphK1 activation was found to be critical for the redox-dependent activation of HIF-1α and ASK1, as well as for the prevention of LPS-induced activation of caspase 3 and the expression of pro-inflammatory cytokine interleukin-6 |
Keywords: | sphingosine kinase 1 inflammation hypoxia-inducible factor 1 pro-inflammatory cytokines apoptosis |
Rights: | © 2011 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. |
DOI: | 10.1038/icb.2010.91 |
Published version: | http://dx.doi.org/10.1038/icb.2010.91 |
Appears in Collections: | Aurora harvest 5 Molecular and Biomedical Science publications |
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