Toll-like receptors activate programmed necrosis in macrophages through a receptor-interacting kinase-3–mediated pathway
Autor: | Sudan He, Yuqiong Liang, Xiaodong Wang, Feng Shao |
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Rok vydání: | 2011 |
Předmět: |
Lipopolysaccharides
Necroptosis Biology Proinflammatory cytokine Mice Necrosis RIPK1 Animals Mice Knockout Multidisciplinary Innate immune system Macrophages Models Immunological NF-kappa B Biological Sciences Protein Structure Tertiary Toll-Like Receptor 3 Cell biology Enzyme Activation Toll-Like Receptor 4 Adaptor Proteins Vesicular Transport TRIF Receptor-Interacting Protein Serine-Threonine Kinases TLR3 TLR4 Cytokines Interferon Regulatory Factor-3 Inflammation Mediators Signal transduction Reactive Oxygen Species Protein Binding Signal Transduction |
Zdroj: | Proceedings of the National Academy of Sciences. 108:20054-20059 |
ISSN: | 1091-6490 0027-8424 |
Popis: | We report here that mouse macrophages undergo receptor-interacting kinase-3 (RIP3)-dependent but TNF-α–independent necrosis when Toll-like receptors (TLR) 3 and 4 are activated by poly(I:C) and LPS, respectively. An adaptor protein, Toll/IL-1 receptor domain-containing adapter inducing IFN-β (TRIF/TICAM-1), which is dispensable for TNF-α–induced necrosis, forms a complex with RIP3 upon TLR3/TLR4 activation and is essential for TLR3/TLR4-induced necrosis. Mice without RIP3 or functional TRIF did not show macrophage loss and elevation of inflammatory cytokines when they were exposed to LPS. Necrosis in mouse macrophages induced by either TNFR or TLR3/TLR4 is executed by reactive oxygen species. Taken together, these data indicate that there are multiple upstream necrosis-initiating signaling pathways converging on the RIP3 during an innate immune response to viral and bacterial infections in mammals. |
Databáze: | OpenAIRE |
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