Inhibition of AIM2 inflammasome-mediated pyroptosis by Andrographolide contributes to amelioration of radiation-induced lung inflammation and fibrosis.

Abstract:

:Radiation-induced lung injury (RILI) is one of the most common and fatal complications of thoracic radiotherapy, whereas no effective interventions are available. Andrographolide, an active component extracted from Andrographis paniculate, is prescribed as a treatment for upper respiratory tract infection. Here we report the potential radioprotective effect and mechanism of Andrographolide on RILI. C57BL/6 mice were exposed to 18 Gy of whole thorax irradiation, followed by intraperitoneal injection of Andrographolide every other day for 4 weeks. Andrographolide significantly ameliorated radiation-induced lung tissue damage, inflammatory cell infiltration, and pro-inflammatory cytokine release in the early phase and progressive fibrosis in the late phase. Moreover, Andrographolide markedly hampered radiation-induced activation of the AIM2 inflammasome and pyroptosis in vivo. Furthermore, bone marrow-derived macrophages (BMDMs) were exposed to 8 Gy of X-ray radiation in vitro and Andrographolide significantly inhibited AIM2 inflammasome mediated-pyroptosis in BMDMs. Mechanistically, Andrographolide effectively prevented AIM2 from translocating into the nucleus to sense DNA damage induced by radiation or chemotherapeutic agents in BMDMs. Taken together, Andrographolide ameliorates RILI by suppressing AIM2 inflammasome mediated-pyroptosis in macrophage, identifying Andrographolide as a novel potential protective agent for RILI.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Gao J,Peng S,Shan X,Deng G,Shen L,Sun J,Jiang C,Yang X,Chang Z,Sun X,Feng F,Kong L,Gu Y,Guo W,Xu Q,Sun Y

doi

10.1038/s41419-019-2195-8

subject

Has Abstract

pub_date

2019-12-20 00:00:00

pages

957

issue

12

issn

2041-4889

pii

10.1038/s41419-019-2195-8

journal_volume

10

pub_type

杂志文章
  • CHD1L contributes to cisplatin resistance by upregulating the ABCB1-NF-κB axis in human non-small-cell lung cancer.

    abstract::Chromodomain helicase/ATPase DNA binding protein 1-like gene (CHD1L) is a recently identified gene associated with malignant tumor progression and patient chemotherapy resistance in human hepatocellular carcinoma (HCC). Previously, we found an association between CHD1L overexpression and poor patient survival in non-s...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1371-1

    authors: Li Y,He LR,Gao Y,Zhou NN,Liu Y,Zhou XK,Liu JF,Guan XY,Ma NF,Xie D

    更新日期:2019-02-04 00:00:00

  • Knockdown of BAG3 induces epithelial-mesenchymal transition in thyroid cancer cells through ZEB1 activation.

    abstract::The process by which epithelial features are lost in favor of a mesenchymal phenotype is referred to as epithelial-mesenchymal transition (EMT). Most carcinomas use this mechanism to evade into neighboring tissues. Reduction or a loss of E-cadherin expression is a well-established hallmark of EMT. As a potent suppress...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2014.32

    authors: Meng X,Kong DH,Li N,Zong ZH,Liu BQ,Du ZX,Guan Y,Cao L,Wang HQ

    更新日期:2014-02-27 00:00:00

  • IFN-γ promoted exosomes from mesenchymal stem cells to attenuate colitis via miR-125a and miR-125b.

    abstract::Bone marrow mesenchymal stem cells (MSCs) have demonstrated therapeutic effects for colitis through immunomodulation and anti-inflammation. However, whether MSC-derived exosomes possessed the similar function remains unclear. In present study, exosomes were isolated from control and IFN-γ-primed MSCs and was verified ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-02788-0

    authors: Yang R,Huang H,Cui S,Zhou Y,Zhang T,Zhou Y

    更新日期:2020-07-30 00:00:00

  • Increase in HDAC9 suppresses myoblast differentiation via epigenetic regulation of autophagy in hypoxia.

    abstract::Extremely reduced oxygen (O2) levels are detrimental to myogenic differentiation and multinucleated myotube formation, and chronic exposure to high-altitude hypoxia has been reported to be an important factor in skeletal muscle atrophy. However, how chronic hypoxia causes muscle dysfunction remains unknown. In the pre...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1763-2

    authors: Zhang Z,Zhang L,Zhou Y,Li L,Zhao J,Qin W,Jin Z,Liu W

    更新日期:2019-07-18 00:00:00

  • A long non-coding RNA interacts with Gfra1 and maintains survival of mouse spermatogonial stem cells.

    abstract::Spermatogonial stem cells (SSCs) are unique male germline stem cells that support spermatogenesis and male fertility. Long non-coding RNAs (lncRNA) have been identified as key regulators of stem cell fate; however, their role in SSCs has not been explored. Here, we report that a novel spermatogonia-specific lncRNA (ln...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2016.24

    authors: Li L,Wang M,Wang M,Wu X,Geng L,Xue Y,Wei X,Jia Y,Wu X

    更新日期:2016-03-10 00:00:00

  • 2,4,5-Trimethoxyldalbergiquinol promotes osteoblastic differentiation and mineralization via the BMP and Wnt/β-catenin pathway.

    abstract::Dalbergia odorifera has been traditionally used as a medicine to treat many diseases. However, the role of 2,4,5-trimethoxyldalbergiquinol (TMDQ) isolated and extracted from D. odorifera in osteoblast function and the underlying molecular mechanisms remain poorly understood. The aim of this study was to investigate th...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2015.185

    authors: Yun HM,Park KR,Quang TH,Oh H,Hong JT,Kim YC,Kim EC

    更新日期:2015-07-16 00:00:00

  • The long non-coding RNA SNHG1 promotes glioma progression by competitively binding to miR-194 to regulate PHLDA1 expression.

    abstract::Long non-coding RNAs (lncRNAs) play a vital role in tumourigenesis, including that of glioma. Small nucleolar RNA host gene 1 (SNHG1) is a relatively novel lncRNA that is involved in the development of multiple human tumours. However, its underlying molecular mechanism in glioma has not been completely clarified. In t...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1698-7

    authors: Liu L,Shi Y,Shi J,Wang H,Sheng Y,Jiang Q,Chen H,Li X,Dong J

    更新日期:2019-06-12 00:00:00

  • Ankrd2 is a modulator of NF-κB-mediated inflammatory responses during muscle differentiation.

    abstract::Adaptive responses of skeletal muscle regulate the nuclear shuttling of the sarcomeric protein Ankrd2 that can transduce different stimuli into specific adaptations by interacting with both structural and regulatory proteins. In a genome-wide expression study on Ankrd2-knockout or -overexpressing primary proliferating...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.525

    authors: Bean C,Verma NK,Yamamoto DL,Chemello F,Cenni V,Filomena MC,Chen J,Bang ML,Lanfranchi G

    更新日期:2014-01-16 00:00:00

  • Metabolism addiction in pancreatic cancer.

    abstract::Pancreatic ductal adenocarcinoma, an aggressively invasive, treatment-resistant malignancy and the fourth leading cause of cancer deaths in the United States, is usually detectable only when already inevitably fatal. Despite advances in genetic screening, mapping and molecular characterization, its pathology remains l...

    journal_title:Cell death & disease

    pub_type: 杂志文章,评审

    doi:10.1038/cddis.2014.38

    authors: Blum R,Kloog Y

    更新日期:2014-02-20 00:00:00

  • Functional validation of a human GLUD2 variant in a murine model of Parkinson's disease.

    abstract::Parkinson's disease (PD) is a common neurodegenerative disease characterized by Lewy body formation and progressive dopaminergic neuron death in the substantia nigra (SN). Genetic susceptibility is a strong risk factor for PD. Previously, a rare gain-of-function variant of GLUD2 glutamate dehydrogenase (T1492G) was re...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-03043-2

    authors: Zhang W,Gong J,Ding L,Zhang Z,Pan X,Chen X,Guo W,Zhang X,Yang X,Peng G,Lin Y,Gao F,Li Y,Zhu X,Xuan A,Wang S,Sun X,Zhang Y,Xu P

    更新日期:2020-10-22 00:00:00

  • CD10-/ALDH- cells are the sole cisplatin-resistant component of a novel ovarian cancer stem cell hierarchy.

    abstract::It is long established that tumour-initiating cancer stem cells (CSCs) possess chemoresistant properties. However, little is known of the mechanisms involved, particularly with respect to the organisation of CSCs as stem-progenitor-differentiated cell hierarchies. Here we aimed to elucidate the relationship between CS...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2017.379

    authors: Ffrench B,Gasch C,Hokamp K,Spillane C,Blackshields G,Mahgoub TM,Bates M,Kehoe L,Mooney A,Doyle R,Doyle B,O'Donnell D,Gleeson N,Hennessy BT,Stordal B,O'Riain C,Lambkin H,O'Toole S,O'Leary JJ,Gallagher MF

    更新日期:2017-10-19 00:00:00

  • Agonist antibodies activating the Met receptor protect cardiomyoblasts from cobalt chloride-induced apoptosis and autophagy.

    abstract::Met, the tyrosine kinase receptor for hepatocyte growth factor (HGF), mainly activates prosurvival pathways, including protection from apoptosis. In this work, we investigated the cardioprotective mechanisms of Met activation by agonist monoclonal antibodies (mAbs). Cobalt chloride (CoCl2), a chemical mimetic of hypox...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2014.155

    authors: Gallo S,Gatti S,Sala V,Albano R,Costelli P,Casanova E,Comoglio PM,Crepaldi T

    更新日期:2014-04-17 00:00:00

  • Inhibition of ER stress-mediated apoptosis in macrophages by nuclear-cytoplasmic relocalization of eEF1A by the HIV-1 Nef protein.

    abstract::HIV-1 Nef protein has key roles at almost all stages of the viral life cycle. We assessed the role of the Nef/eEF1A (eukaryotic translation elongation factor 1-alpha) complex in nucleocytoplasmic shuttling in primary human macrophages. Nuclear retention experiments and inhibition of the exportin-t (Exp-t) pathway sugg...

    journal_title:Cell death & disease

    pub_type: 杂志文章,收录出版

    doi:10.1038/cddis.2012.32

    authors: Abbas W,Khan KA,Tripathy MK,Dichamp I,Keita M,Rohr O,Herbein G

    更新日期:2012-04-05 00:00:00

  • Inhibitor of apoptosis proteins are required for effective fusion of autophagosomes with lysosomes.

    abstract::Inhibitor of Apoptosis Proteins act as E3 ubiquitin ligases to regulate NF-κB signalling from multiple pattern recognition receptors including NOD2, as well as TNF Receptor Superfamily members. Loss of XIAP in humans causes X-linked Lymphoproliferative disease type 2 (XLP-2) and is often associated with Crohn's diseas...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0508-y

    authors: Gradzka S,Thomas OS,Kretz O,Haimovici A,Vasilikos L,Wong WW,Häcker G,Gentle IE

    更新日期:2018-05-01 00:00:00

  • Tumor suppressor death-associated protein kinase 1 inhibits necroptosis by p38 MAPK activation.

    abstract::Death-associated protein kinase 1 (DAPK1, DAPk, DAPK) is known for its involvement in apoptosis and autophagy-associated cell death. Here, we identified an unexpected function of DAPK1 in suppressing necroptosis. DAPK1-deficiency renders macrophages and dendritic cells susceptible to necroptotic death. We also observe...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-2534-9

    authors: Wu YH,Chou TF,Young L,Hsieh FY,Pan HY,Mo ST,Brown SB,Chen RH,Kimchi A,Lai MZ

    更新日期:2020-05-04 00:00:00

  • DEPTOR is a direct p53 target that suppresses cell growth and chemosensitivity.

    abstract::DEP-domain containing mTOR-interacting protein (DEPTOR), a natural mTOR inhibitor, has essential roles in several processes, including cell growth, metabolism, apoptosis, and immunity. DEPTOR expression has been shown to be diversely controlled at transcriptional levels in cell- and context-specific manners. However, ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-03185-3

    authors: Cui D,Dai X,Gong L,Chen X,Wang L,Xiong X,Zhao Y

    更新日期:2020-11-12 00:00:00

  • Involvement of lipid rafts in the localization and dysfunction effect of the antitumor ether phospholipid edelfosine in mitochondria.

    abstract::Lipid rafts and mitochondria are promising targets in cancer therapy. The synthetic antitumor alkyl-lysophospholipid analog edelfosine (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) has been reported to target lipid rafts. Here, we have found that edelfosine induced loss of mitochondrial membrane potential an...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2011.41

    authors: Mollinedo F,Fernández M,Hornillos V,Delgado J,Amat-Guerri F,Acuña AU,Nieto-Miguel T,Villa-Pulgarín JA,González-García C,Ceña V,Gajate C

    更新日期:2011-05-19 00:00:00

  • NudCL2 regulates cell migration by stabilizing both myosin-9 and LIS1 with Hsp90.

    abstract::Cell migration plays pivotal roles in many biological processes; however, its underlying mechanism remains unclear. Here, we find that NudC-like protein 2 (NudCL2), a cochaperone of heat shock protein 90 (Hsp90), modulates cell migration by stabilizing both myosin-9 and lissencephaly protein 1 (LIS1). Either knockdown...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-02739-9

    authors: Chen W,Wang W,Sun X,Xie S,Xu X,Liu M,Yang C,Li M,Zhang W,Liu W,Wang L,Zhou T,Yang Y

    更新日期:2020-07-14 00:00:00

  • Mkk4 and Mkk7 are important for retinal development and axonal injury-induced retinal ganglion cell death.

    abstract::The mitogen-activated protein kinase (MAPK) pathway has been shown to be involved in both neurodevelopment and neurodegeneration. c-Jun N-terminal kinase (JNK), a MAPK important in retinal development and after optic nerve crush injury, is regulated by two upstream kinases: MKK4 and MKK7. The specific requirements of ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-1079-7

    authors: Syc-Mazurek SB,Rausch RL,Fernandes KA,Wilson MP,Libby RT

    更新日期:2018-10-26 00:00:00

  • miR-340-FHL2 axis inhibits cell growth and metastasis in ovarian cancer.

    abstract::Although increasing evidence indicated that deregulation of microRNAs (miRNAs) contributed to tumor initiation and progression, but little is known about the biological role of miR-340 in ovarian cancer (OC). In this study, we found that miR-340 expression was downregulated in OC tissues compared with its expression i...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1604-3

    authors: Huang Z,Li Q,Luo K,Zhang Q,Geng J,Zhou X,Xu Y,Qian M,Zhang JA,Ji L,Wu J

    更新日期:2019-05-08 00:00:00

  • Drp1 regulates mitochondrial dysfunction and dysregulated metabolism in ischemic injury via Clec16a-, BAX-, and GSH- pathways.

    abstract::The adaptation of mitochondrial homeostasis to ischemic injury is not fully understood. Here, we studied the role of dynamin-related protein 1 (Drp1) in this process. We found that mitochondrial morphology was altered in the early stage of ischemic injury while mitochondrial dysfunction occurred in the late stage of i...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-2461-9

    authors: Duan C,Kuang L,Xiang X,Zhang J,Zhu Y,Wu Y,Yan Q,Liu L,Li T

    更新日期:2020-04-20 00:00:00

  • Inhibition of Casein kinase-2 induces p53-dependent cell cycle arrest and sensitizes glioblastoma cells to tumor necrosis factor (TNFα)-induced apoptosis through SIRT1 inhibition.

    abstract::Glioblastoma multiforme (GBM) are resistant to TNFα-induced apoptosis and blockade of TNFα-induced NF-κB activation sensitizes glioma cells to apoptosis. As Casein kinase-2 (CK2) induces aberrant NF-κB activation and as we observed elevated CK2 levels in GBM tumors, we investigated the potential of CK2 inhibitors (CK2...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2012.10

    authors: Dixit D,Sharma V,Ghosh S,Mehta VS,Sen E

    更新日期:2012-02-09 00:00:00

  • Multiple mechanisms mediating carbon monoxide inhibition of the voltage-gated K+ channel Kv1.5.

    abstract::The voltage-gated K+ channel has key roles in the vasculature and in atrial excitability and contributes to apoptosis in various tissues. In this study, we have explored its regulation by carbon monoxide (CO), a product of the cytoprotective heme oxygenase enzymes, and a recognized toxin. CO inhibited recombinant Kv1....

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2017.568

    authors: Al-Owais MM,Hettiarachchi NT,Boyle JP,Scragg JL,Elies J,Dallas ML,Lippiat JD,Steele DS,Peers C

    更新日期:2017-11-02 00:00:00

  • Protease-activated receptor 2 signaling modulates susceptibility of colonic epithelium to injury through stabilization of YAP in vivo.

    abstract::Hippo signaling plays critical roles in intestinal regeneration. However, the mechanisms which regulate its activity in vivo are largely unknown. We hypothesize that protease-activated receptor 2 (PAR2) signaling, which could be activated by trypsin, might affect YAP activity in the setting of tissue damage and regene...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0995-x

    authors: He L,Ma Y,Li W,Han W,Zhao X,Wang H

    更新日期:2018-09-20 00:00:00

  • Modified CAR T cells targeting membrane-proximal epitope of mesothelin enhances the antitumor function against large solid tumor.

    abstract::Mesothelin (MSLN) is an attractive antigen for chimeric antigen receptor (CAR) T therapy and the epitope selection within MSLN is essential. In this study, we constructed two types of CARs targeting either region I of MSLN (meso1 CAR, also known as a membrane-distal region) or region III of MSLN (meso3 CAR, also known...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1711-1

    authors: Zhang Z,Jiang D,Yang H,He Z,Liu X,Qin W,Li L,Wang C,Li Y,Li H,Xu H,Jin H,Qian Q

    更新日期:2019-06-17 00:00:00

  • Long non-coding RNA H19 confers 5-Fu resistance in colorectal cancer by promoting SIRT1-mediated autophagy.

    abstract::Chemotherapy failure is the major cause of recurrence and poor prognosis in colorectal cancer (CRC) patients. The role of the differentially expressed lncRNAs in 5-Fluorouracil chemoresistance has not fully explained. Here, we observed lncRNA H19 was associated with the 5-Fu resistance in CRC. Quantitative analysis in...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-1187-4

    authors: Wang M,Han D,Yuan Z,Hu H,Zhao Z,Yang R,Jin Y,Zou C,Chen Y,Wang G,Gao X,Wang X

    更新日期:2018-11-19 00:00:00

  • Phosphorylation of cyclophilin D at serine 191 regulates mitochondrial permeability transition pore opening and cell death after ischemia-reperfusion.

    abstract::The mitochondrial permeability transition pore (mPTP) plays a critical role in the pathogenesis of cardiovascular diseases, including ischemia/reperfusion injury. Although the pore structure is still unresolved, the mechanism through which cyclophilin D (CypD) regulates mPTP opening is the subject of intensive studies...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-02864-5

    authors: Hurst S,Gonnot F,Dia M,Crola Da Silva C,Gomez L,Sheu SS

    更新日期:2020-08-19 00:00:00

  • Correction: Mechanism of Snhg8/miR-384/Hoxa13/FAM3A axis regulating neuronal apoptosis in ischemic mice model.

    abstract::Following the publication of this article, the authors realized there was an error in Figure 6H in which two versions of the figure appear.This does not impact the conclusions of the article. ...

    journal_title:Cell death & disease

    pub_type: 已发布勘误

    doi:10.1038/s41419-019-1865-x

    authors: Liu J,An P,Xue Y,Che D,Liu X,Zheng J,Liu Y,Yang C,Li Z,Yu B

    更新日期:2019-08-21 00:00:00

  • WDR79 promotes the proliferation of non-small cell lung cancer cells via USP7-mediated regulation of the Mdm2-p53 pathway.

    abstract::WD repeat protein 79 (WDR79) is a member of the WD-repeat protein family and functions as a scaffold protein during telomerase assembly, Cajal body formation and DNA double strand break repair. We have previously shown that WDR79 is frequently overexpressed in cell lines and tissues derived from non-small cell lung ca...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2017.162

    authors: Sun Y,Cao L,Sheng X,Chen J,Zhou Y,Yang C,Deng T,Ma H,Feng P,Liu J,Tan W,Ye M

    更新日期:2017-04-13 00:00:00

  • Autophagy activated by silibinin contributes to glioma cell death via induction of oxidative stress-mediated BNIP3-dependent nuclear translocation of AIF.

    abstract::Induction of lethal autophagy has become a strategy to eliminate glioma cells, but it remains elusive whether autophagy contributes to cell death via causing mitochondria damage and nuclear translocation of apoptosis inducing factor (AIF). In this study, we find that silibinin induces AIF translocation from mitochondr...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-02866-3

    authors: Wang C,He C,Lu S,Wang X,Wang L,Liang S,Wang X,Piao M,Cui J,Chi G,Ge P

    更新日期:2020-08-14 00:00:00