LPS-induced Toll-like receptor 4 signalling triggers cross-talk of apoptosis signal-regulating kinase 1 (ASK1) and HIF-1α protein

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Abstract

Toll-like receptor 4 (TLR4) is required for recognition of lipopolysaccharide (LPS) of Gram-negative bacteria and induction of the innate immune response to them. Nevertheless, the involvement of some crucial pathways in TLR4 signalling is poorly understood. Here, we report that LPS-induced TLR4 signalling triggers cross talk of HIF-1α and ASK1 in THP-1 human myeloid monocytic leukaemia cells. Both pathways are activated via redox-dependent mechanism associated with tyrosine kinase/phospholipase C-1γ-mediated activation of protein kinase C α/β, which are known to activate NADPH oxidase and the production of reactive oxygen species that activate both HIF-1α and ASK1. ASK1 contributes to the stabilisation of HIF-1α, most likely via activation of p38 MAP kinase. © 2007 Federation of European Biochemical Societies.

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Sumbayev, V. V. (2008). LPS-induced Toll-like receptor 4 signalling triggers cross-talk of apoptosis signal-regulating kinase 1 (ASK1) and HIF-1α protein. FEBS Letters, 582(2), 319–326. https://doi.org/10.1016/j.febslet.2007.12.024

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