The Interferon Stimulator Mitochondrial Antiviral Signaling Protein Facilitates Cell Death by Disrupting the Mitochondrial Membrane Potential and by Activating Caspases

Yu, Chia-Yi; Chiang, Ruei-Lin; Chang, Tsung-Hsien; Liao, Ching‐Len; Lin, Yi-Ling

doi:10.1128/jvi.02174-09

Cited by 60 publications

(74 citation statements)

References 46 publications

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“…Therefore, it is possible that the radiosensitizing effect of poly(I:C)-HMW and the effects of poly(I:C)-HMW and ionizing radiation cotreatment on cytotoxicity are due to the induction of type I IFN. However, because it is reported that RLR/MAVS signaling pathway induces apoptosis in a IFN-independent manner (7,25,26), we need a further study to clarify whether the effects of RLR agonist and ionizing radiation cotreatment on cytotoxicity depends on the type I IFN.…”

Section: Discussionmentioning

confidence: 99%

Effects of retinoic acid-inducible gene-I-like receptors activations and ionizing radiation cotreatment on cytotoxicity against human non-small cell lung cancer inï¿½vitro

et al. 2018

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Abstract. Retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) are pattern-recognition receptors that recognize pathogen-associated molecular patterns and induce antiviral immune responses. Recent studies have demonstrated that RLR activation induces antitumor immunity and cytotoxicity against different types of cancer, including lung cancer. However a previous report has demonstrated that ionizing radiation exerts a limited effect on RLR in human monocytic cell-derived macrophages, suggesting that RLR agonists may be used as effective immunostimulants during radiation therapy. However, it is unclear whether ionizing radiation affects the cytotoxicity of RLR agonists against cancer cells. Therefore, in the present study the effects of cotreatment with ionizing radiation and RLR agonists on cytotoxicity against human non-small cell lung cancer cells A549 and H1299 was investigated. Treatment with RLR agonist poly(I:C)/LyoVec™ [poly(I:C)] exerted cytotoxic effects against human non-small cell lung cancer. The cytotoxic effects of poly(I:C) were enhanced by cotreatment with ionizing radiation, and poly(I:C) pretreatment resulted in the radiosensitization of non-small cell lung cancer. Furthermore, cotreatment of A549 and H1299 cells with poly(I:C) and ionizing radiation effectively induced apoptosis in a caspase-dependent manner compared with treatment with poly(I:C) or ionizing radiation alone. These results indicate that RLR agonists and ionizing radiation cotreatment effectively exert cytotoxic effects against human non-small cell lung cancer through caspase-mediated apoptosis.

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Section: Discussionmentioning

confidence: 99%

Effects of retinoic acid-inducible gene-I-like receptors activations and ionizing radiation cotreatment on cytotoxicity against human non-small cell lung cancer inï¿½vitro

et al. 2018

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“…35 Caspase-1-dependent IL-18 cleavage was also previously reported. 36 In addition, activation of the NLRP3-inflammasome was recently demonstrated in DV-infected macrophages in culture. 16 Assembly of NLRP3 inflammasomes has also been described in other viral infections, including those by the DV family flavivirus.…”

Section: Discussionmentioning

confidence: 99%

Platelets mediate increased endothelium permeability in dengue through NLRP3-inflammasome activation

Hottz

Lopes

Freitas

et al. 2013

Blood

298

380

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• Dengue infection triggers functional inflammasome assembly in platelets.• Platelets may contribute to increased vascular permeability in dengue virus infection by synthesis and release of IL-1b.Dengue is the most frequent hemorrhagic viral disease and re-emergent infection in the world. Although thrombocytopenia is characteristically observed in mild and severe forms of dengue, the role of platelet activation in dengue pathogenesis has not been fully elucidated. We hypothesize that platelets have major roles in inflammatory amplification and increased vascular permeability during severe forms of dengue. Here we investigate interleukin (IL)-1b synthesis, processing, and secretion in platelets during dengue virus (DV) infection and potential contribution of these events to endothelial permeability during infection. We observed increased expression of IL-1b in platelets and plateletderived microparticles from patients with dengue or after platelet exposure to DV in vitro. We demonstrated that DV infection leads to assembly of nucleotide-binding domain leucine rich repeat containing protein (NLRP3) inflammasomes, activation of caspase-1, and caspase-1-dependent IL-1b secretion. Our findings also indicate that plateletderived IL-1b is chiefly released in microparticles through mechanisms dependent on mitochondrial reactive oxygen speciestriggered NLRP3 inflammasomes. Inflammasome activation and platelet shedding of IL-1b-rich microparticles correlated with signs of increased vascular permeability. Moreover, microparticles from DV-stimulated platelets induced enhanced permeability in vitro in an IL-1-dependent manner. Our findings provide new evidence that platelets contribute to increased vascular permeability in DV infection by inflammasome-dependent release of IL-1b. (Blood. 2013;122(20):3405-3414)

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“…Although MAM-localized MAVS directs innate immunity against HCV, our observations do not exclude a role for mitochondrial MAVS in innate immune signaling. In this respect, mitochondrial MAVS supports apoptotic signaling of innate immune actions against virus infection (31,32), and also could serve as a local source of MAVS for distribution among peroxisomes and MAM through dynamic membrane trafficking regulated by MFN2. This latter idea is supported by previous work showing that peroxisomes are not required for populating mitochondria with MAVS (6), suggesting that peroxisomes may receive MAVS by membrane trafficking through MAM-mitochondrial interactions.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial-associated endoplasmic reticulum membranes (MAM) form innate immune synapses and are targeted by hepatitis C virus

Horner

Liu

Park

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

441

460

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RIG-I is a cytosolic pathogen recognition receptor that engages viral RNA in infected cells to trigger innate immune defenses through its adaptor protein MAVS. MAVS resides on mitochondria and peroxisomes, but how its signaling is coordinated among these organelles has not been defined. Here we show that a major site of MAVS signaling is the mitochondrial-associated membrane (MAM), a distinct membrane compartment that links the endoplasmic reticulum to mitochondria. During RNA virus infection, RIG-I is recruited to the MAM to bind MAVS. Dynamic MAM tethering to mitochondria and peroxisomes then coordinates MAVS localization to form a signaling synapse between membranes. Importantly, the hepatitis C virus NS3/4A protease, which cleaves MAVS to support persistent infection, targets this synapse for MAVS proteolysis from the MAM, but not from mitochondria, to ablate RIG-I signaling of immune defenses. Thus, the MAM mediates an intracellular immune synapse that directs antiviral innate immunity.interferon | IPS-1

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The Interferon Stimulator Mitochondrial Antiviral Signaling Protein Facilitates Cell Death by Disrupting the Mitochondrial Membrane Potential and by Activating Caspases

Cited by 60 publications

References 46 publications

Effects of retinoic acid-inducible gene-I-like receptors activations and ionizing radiation cotreatment on cytotoxicity against human non-small cell lung cancer inï¿½vitro

Effects of retinoic acid-inducible gene-I-like receptors activations and ionizing radiation cotreatment on cytotoxicity against human non-small cell lung cancer inï¿½vitro

Platelets mediate increased endothelium permeability in dengue through NLRP3-inflammasome activation

Mitochondrial-associated endoplasmic reticulum membranes (MAM) form innate immune synapses and are targeted by hepatitis C virus

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