RIPK3 Activation Leads to Cytokine Synthesis that Continues after Loss of Cell Membrane Integrity
| Autor: | Haiyin Chen-Harris, Pooja Ralli-Jain, Sharon Frase, Douglas R. Green, Annelise G. Snyder, Susana Orozco, Stephen W.G. Tait, Brian P. Daniels, Andrew Oberst, Nader Yatim, Sean P. Cullen, Giovanni Quarato, Michelle N. Messmer, Matthew L. Albert |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Chemokine Programmed cell death Necroptosis medicine.medical_treatment Cell Endoplasmic Reticulum General Biochemistry Genetics and Molecular Biology Article Cell membrane 03 medical and health sciences Mice 0302 clinical medicine Immune system medicine Animals RNA Messenger lcsh:QH301-705.5 Innate immune system biology Chemistry Tumor Necrosis Factor-alpha Cell Membrane 3T3 Cells Cell biology Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Cytokine lcsh:Biology (General) Receptor-Interacting Protein Serine-Threonine Kinases biology.protein Female 030217 neurology & neurosurgery |
| Zdroj: | Cell Reports, Vol 28, Iss 9, Pp 2275-2287.e5 (2019) |
| ISSN: | 2211-1247 |
| Popis: | Summary: Necroptosis is a form of programmed cell death that is defined by activation of the kinase RIPK3 and subsequent cell membrane permeabilization by the effector MLKL. RIPK3 activation can also promote immune responses via production of cytokines and chemokines. How active cytokine production is coordinated with the terminal process of necroptosis is unclear. Here, we report that cytokine production continues within necroptotic cells even after they have lost cell membrane integrity and irreversibly committed to death. This continued cytokine production is dependent on mRNA translation and requires maintenance of endoplasmic reticulum integrity that remains after plasma membrane integrity is lost. The continued translation of cytokines by cellular corpses contributes to necroptotic cell uptake by innate immune cells and priming of adaptive immune responses to antigens associated with necroptotic corpses. These findings imply that cell death and production of inflammatory mediators are coordinated to optimize the immunogenicity of necroptotic cells. : Necroptotic cell death is associated with cytokine production. Orozco et al. show that necroptotic cell “corpses” continue to synthesize cytokines after they have lost membrane integrity and committed to cell death. This activity involves continued mRNA translation and requires ER function that continues after plasma membrane rupture. Keywords: necroptosis, cell death, phagocytosis, cytokines, RIPK3, MLKL |
| Databáze: | OpenAIRE |
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