Myeloid cell death associated with Toll-like receptor 7/8-mediated inflammatory response. Implication of ASK1, HIF-1 alpha, IL-1 beta and TNF-alpha.
Programmed cell death or apoptosis is an important part of the host innate immune defence, especially against ssRNA viruses (influenza virus, HIV-1, ebola virus, hepatitis C virus and many others). Viral ssRNA is recognised by endosomal Toll-like receptors 7 and 8 (TLR7/8) which induce further stages of immune defence against these pathogens. Some of the immune cells die because of inflammatory stress allowing for the selection of those cells which are resistant to stress-induced apoptosis and which are used in further stages of the host immune response. On the other hand, apoptosis could be used as an instrument to suppress the function of activated inflammatory cells. However, the mechanisms underlying death of the inflammatory cells associated with stress induced by ligands of TLR7/8 remain unclear. In this study we have found that programmed death of human myeloid cells from different cell lines associated with ligand-induced TLR7/8-mediated inflammatory stress depends on activation of apoptosis signal-regulating kinase 1 (ASK1). This enzyme is, however, not required for the production of pro-inflammatory cytokines - TNF-α and IL-1β. We have found that released IL-1β and TNF-α are involved in apoptosis of myeloid cells associated with TLR7/8-mediated inflammatory stress. The pro-apoptotic effect of released TNF-α in this case is much lower compared to that of IL-1β.
Nicholas
Sally A
SA
Medway School of Pharmacy, University of Kent, Kent, United Kingdom.
Oniku
Abraham E
AE
Sumbayev
Vadim V
VV
D017209:Apoptosis / Q000276:immunology*; D015153:Blotting, Western; D002460:Cell Line; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism; D048848:MAP Kinase Kinase Kinase 5 / Q000276:immunology / Q000378:metabolism; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000276:immunology* / Q000378:metabolism; D051200:Toll-Like Receptor 8 / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D053583:Interleukin-1beta; C495348:TLR7 protein, human; C495349:TLR8 protein, human; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D014409:Tumor Necrosis Factor-alpha; D048848:MAP Kinase Kinase Kinase 5